Biocontrol Agents and Secondary Metabolites: Applications and Immunization for Plant Growth and Protection

By Sudisha Jogaiah

Biocontrol and Secondary Metabolites: Applications and Immunization for Plant Growth and Protection covers established and updated research on emerging trends in plant defense signaling in, and during, stress phases. Other topics cover growth at interface as a sustainable way of life and the context of human welfare and conservation of fungi as a group of organisms. Further, the book explores induced systemic resistance using biocontrol agents and/or secondary metabolites as a milestone for sustainable agricultural production, thus providing opportunities for the minimization or elimination of the use of fungicides.

• Presents an overview on mechanisms by which plants protect themselves against herbivory and pathogenic microbes
• Identifies the use of immunization as a popular and effective alternative to chemical pesticides
• Explores how these fungi help crop plants in better uptake of soil nutrients, increase soil fertility, produce growth promoting substances, and secrete metabolites that act as bio-pesticides

• Language: English
• Publisher: Elsevier Science
• Release date: Nov 13, 2020
• ISBN: 9780128230947

Book preview

Biocontrol Agents and Secondary Metabolites

Applications and Immunization for Plant Growth and Protection

First Edition

Sudisha Jogaiah

Laboratory of Plant Healthcare and Diagnostics, P.G. Department of Biotechnology and Microbiology, Karnatak University, Dharwad, Karnataka, India

Table of Contents

Cover image

Title page

Copyright

Dedication

Contributors

About the editor

Foreword

Preface

Acknowledgments

Introduction

1: Fungi endophytes for biofactory of secondary metabolites: Genomics and metabolism

Abstract

Acknowledgments

1.1: Introduction

1.2: Fungal endophytes frequency and transmission in plant organizations

1.3: Endophytic fungus as biofactory of bioactive compounds

1.4: Genome level secondary metabolism metabolic modeling

1.5: Gene clusters for fungal metabolism: Diversity and distribution

1.6: Methodological and technological advancement of genome for metabolites

1.7: Production of SMs by pathway-specific overexpression regulatory genes

1.8: Genetic makeup of fungal secondary metabolism

1.9: Identifying gene clusters of fungi

1.10: Applications for secondary metabolites through genome editing and metabolic engineering

1.11: Perspectives and conclusions

2: Impact of potassium solubilizing fungi as biopesticides and its role in crop improvement

Abstract

2.1: Introduction

2.2: Importance of soil potassium

2.3: Role of potassium in plants

2.4: Role of microorganisms in potassium solubility and uptake

2.5: Role of potassium solubilizing fungi as biofertilizer

2.6: Role of potassium solubilizing fungi as biopesticide/biocontrol agent

2.7: Biocontrol agents

2.8: Mode of action

2.9: Conclusions

3: Trichoderma-plant-pathogen interactions for benefit of agriculture and environment

Abstract

Acknowledgment

3.1: Introduction

3.2: Trichoderma-plant interaction

3.3: Effect on plant physiology, effect on yield and quality of produce

3.4: Induced resistance against biotic and abiotic stresses

3.5: Trichoderma-pathogen interactions

3.6: The three-way interaction: Trichoderma-plant-pathogen

3.7: Future prospects

3.8: Conclusions

4: Trichoderma: From gene to field

Abstract

4.1: Introduction

4.2: Trichoderma-mediated genes and elicitors-induced disease resistance in plant host system

4.3: Trichoderma-based biocontrol formulations

4.4: Trichoderma-based effector molecules: A model system to design specific bioformulations

4.5: Trichoderma effector proteins

4.6: Trichoderma secondary metabolites (SMs)—New effectors in plant interactions

4.7: Plant growth regulators (PGRs)

4.8: Nanotechnology-based Trichoderma formulation: Future trends for the biological control of plant diseases

4.9: Innovative technology beyond the ordinary with synthetic biology interventions: Trichoderma proteomics and metabolomics

5: Potential of Trichoderma species in alleviating the adverse effects of biotic and abiotic stresses in plants

Abstract

5.1: Introduction

5.2: Interaction, colonization, and plant growth promotion by Trichoderma

5.3: Role of Trichoderma spp. in alleviating biotic stress

5.4: Role of Trichoderma spp. in alleviating abiotic stress

5.5: Conclusion

6: Beneficial plant-associated bacteria modulate host hormonal system enhancing plant resistance toward abiotic stress

Abstract

6.1: Introduction

6.2: Plant response and adaptation to the abiotic stress condition

6.3: Abscisic acid (ABA)

6.4: Ethylene (ET)

6.5: Cytokinins (CK)

6.6: Gibberellins (GAs)

6.7: Auxin (AU)

6.8: Strigolactones (SLs)

6.9: Salicylic acid (SA)

6.10: Jasmonic acid (JA)

6.11: Other hormones

6.12: Conclusion and future prospects

7: Biocontrol potential of plant growth-promoting rhizobacteria (PGPR) against Ralstonia solanacearum: Current and future prospects

Abstract

7.1: Introduction

7.2: Mechanisms of plant growth-promoting rhizobacteria against Ralstonia solanacearum

7.3: Conclusion

8: Seed biopriming a novel method to control seed borne diseases of crops

Abstract

8.1: Introduction

8.2: Seed priming

8.3: Biopriming

8.4: The procedure of seed biopriming

8.5: Mechanism of action of seed biopriming by bioagents

8.6: Conclusion and future perspective

9: Metabolomic profile modification and enhanced disease resistance derived from alien genes introgression in plants

Abstract

9.1: Introduction

9.2: Metabolomic modification derived from genetic alteration

9.3: Genetic basis of phytochemical biosynthesis

9.4: Active metabolites as biomarkers for disease resistance in plant breeding

9.5: Conclusion

10: Current trend and future prospects of secondary metabolite-based products from agriculturally important microorganisms

Abstract

Acknowledgments

10.1: Introduction

10.2: Overview of microbial metabolites

10.3: Mining platform and biochemical pathways of secondary metabolites biosynthesis

10.4: Genome mining for secondary metabolites

10.5: Applications

10.6: Conclusion

10.7: Future prospects and concerns

11: Antimicrobial secondary metabolites from Trichoderma spp. as next generation fungicides

Abstract

11.1: Introduction

11.2: Trichoderma as rhizofungi

11.3: Trichoderma CWDE and MAMP molecules on improving plant health

11.4: Molecular patterns of Trichoderma-mediated resistance response

11.5: Nonribosomal peptides and their antifungal activity

11.6: Polygalacturonase ThPG1

11.7: Xylanase Eix/Xyn2

11.8: Cellulases

11.9: Cerato-platanins in ISR and rhizosphere competence

11.10: Swollenin-mediated root colonization and resistance

11.11: Peptaibols: An inducer of signal molecules

11.12: 6-Pentyl pyrones trigger ISR/SAR and plant growth

11.13: Antifungal activity of trichothecenes

11.14: Volatile organic compounds and plant defense

11.15: Antifungal activity of terpenoids

11.16: Lytic enzymes

11.17: Antimicrobial genes of Trichoderma

11.18: Growth promotion by Trichoderma

11.19: Antimicrobial activity of Trichoderma secondary metabolites

11.20: Antimicrobial activity of VOC

11.21: Conclusion

12: Microbial secondary metabolites and their role in stress management of plants

Abstract

12.1: Introduction

12.2: Microbial metabolites

12.3: Conclusion

13: Signatures of signaling pathways underlying plant-growth promotion by fungi

Abstract

Acknowledgment

13.1: Introduction

13.2: Plant-growth promotion (PGP) by fungi (PGPF)

13.3: Molecular mechanisms or cell signaling of plant-growth promotion

13.4: Mycorrhizal fungi (MF) as growth promoter

13.5: Conclusion

14: Overproduction of ROS: underlying molecular mechanism of scavenging and redox signaling

Abstract

14.1: Introduction

14.2: ROS biochemistry

14.3: ROS Production in plant cell

14.4: ROS scavenging by the antioxidant defense system

14.5: Nonenzymatic antioxidants

14.6: ROS in redox signaling

14.7: Conclusion

15: Antioxidant-mediated defense in triggering resistance against biotic stress in plants

Abstract

Acknowledgments

15.1: Introduction

15.2: Early defense responses

15.3: Reactive oxygen species (ROS)

15.4: ROS and reactive nitrogen species (RNS)

15.5: ROS scavenging via the antioxidant system

15.6: Enhancement of ROS scavenging and plant immunity

15.7: Conclusion

16: Role of terpenes in plant defense to biotic stress

Abstract

16.1: Introduction

16.2: Role of terpenes in resistance to fungal diseases

16.3: Role of terpenes in interaction with bacteria

16.4: Role of terpenes in interaction with viruses

16.5: Conclusion

17: Role of phenols and polyphenols in plant defense response to biotic and abiotic stresses

Abstract

17.1: Introduction

17.2: Phenols and polyphenols in crops

17.3: Systemic protection toward biotic and abiotic stresses

17.4: Role of phenols and polyphenols in plant growth

17.5: Conclusion

18: Terpenoid indole alkaloids, a secondary metabolite in plant defense response

Abstract

18.1: Introduction

18.2: Secondary metabolites classification

18.3: Terpenoidindole alkaloid pathway

18.4: Localization of the TIA pathway

18.5: Regulation of the TIA pathway

18.6: Defense responses of TIAs in plants

19: Exploring plant volatile compounds in sustainable crop improvement

Abstract

19.1: Introduction

19.2: PVCs in protection against pathogens

19.3: PVCs in protection against herbivores

19.4: PVC-mediated weed control

19.5: PVCs in improving/suppressing plant growth and productivity

19.6: PVCs in smart agriculture practices

20: Biostimulants: Promising probiotics for plant health

Abstract

20.1: Introduction

20.2: Biostimulant: A changing perspective

20.3: Active components of biostimulant

20.4: Biofilms: A natural consortium

20.5: Future prospects

21: Explorations of fungal diversity in extreme environmental conditions for sustainable agriculture applications

Abstract

21.1: Introduction

21.2: Explorations of fungal diversity

21.3: Conclusion

22: Diversity and functions of secondary metabolites secreted by epi-endophytic microbes and their interaction with phytopathogens

Abstract

22.1: Introduction

22.2: Biocontrol agents (BCAs)

22.3: Epi/endophytes

22.4: Secondary metabolites

22.5: Synthesis pathway and diversity

22.6: Interaction in spermosphere

22.7: Interaction in rhizosphere

22.8: Interaction with postharvest pathogens

22.9: Interaction in phyllosphere

22.10: Epiphytic microflora for plant disease management

22.11: Challenges and future perspectives for upscaling the secondary metabolites

23: Fungal diversity and its role in sustainable agriculture

Abstract

23.1: Introduction

23.2: Classification of fungi

23.3: Well-known groups

23.4: Moderately well-known groups

23.5: Poorly known groups

23.6: Fungi and ecosystems

23.7: Economic value of fungi

23.8: Biodiversity of fungi

23.9: Fungi in sustainable agriculture

23.10: Nutrient recycling

23.11: Mycorrhiza

23.12: Endophytic fungi

23.13: Bioremediation

23.14: Fungi as biocontrol agents

23.15: Conclusion

24: Exploring the biogeographical diversity of Trichoderma for plant health

Abstract

24.1: Introduction

24.2: Is Trichoderma important?

24.3: Attributes of Trichoderma as a successful biocontrol organism

24.4: Ecology of Trichoderma

24.5: Systematics of Trichoderma and its significance in biodiversity

24.6: Global diversity of Trichoderma—An overview

24.7: Species diversity of Trichoderma

24.8: Ecological significance of Trichoderma

24.9: Factors influencing bioefficacy of Trichoderma in maintaining plant health

24.10: Mode of action

24.11: Commercial production and formulations

24.12: Shelf life

24.13: Delivery system

24.14: Population dynamics of Trichoderma

24.15: Strain improvement of Trichoderma

24.16: Industrial application of Trichoderma

24.17: Conclusion

25: Pathogenesis-related proteins: Role in plant defense

Abstract

Acknowledgment

25.1: Introduction

25.2: PR proteins

25.3: Conclusion

26: Different mechanisms of signaling pathways for plant protection from diseases by fungi

Abstract

Acknowledgment

26.1: Introduction

26.2: Plant defense mechanism by utilization of fungi

26.3: Signaling pathways during induced resistance (ISR and SAR)

26.4: Elicitors produced by FBCA

26.5: Transgenic approach for plant protection using BCA genes

26.6: Siderophore in plant immune defense response

26.7: ACCD [1-aminocyclopropane-1-carboxylate (ACC) deaminase] mediated plant defense

26.8: Induction of plant resistance/plant protection mechanisms by mycorrhizal fungi–plant interaction

26.9: Chemical interaction of the mycorrhizal fungi with the host

26.10: Genes and signaling pathway involved in the induction of resistance of host by mycorrhizal fungi

26.11: Yeasts as BCA, induction of disease resistance signaling pathways in host plant

26.12: The three-way talk/interaction analysis: Trichoderma-plant-pathogen

26.13: Conclusion

27: Ecological studies of fungal biodiversity in freshwater and their broad-spectrum applications

Abstract

27.1: Introduction

27.2: Diversity of fungi

27.3: Ecological impact on fungal biodiversity

27.4: Occurrence

27.5: Reproduction

27.6: Uses of fungi

27.7: Significance

28: CRISPR/Cas system: A powerful approach for enhanced resistance against rice blast

Abstract

28.1: Introduction

28.2: Concept-proof demonstration of CRISPR/Cas system in rice

28.3: Engineering rice blast resistance through CRISPR tool-kit

28.4: Perspectives for genome-edited blast-resistant rice

29: Regulatory requirement for commercialization of biocontrol agents

Abstract

Acknowledgment

29.1: Introduction

29.2: Biocontrol agents

29.3: Regulatory requirements: Indian and global perspective

29.4: Summary and conclusion

Annexure. List of efficacious biocontrol agents

Index

Copyright

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Dedication

Laboratory to Farming Community.

Contributors

K.N. Basavesha     Department of Agricultural Microbiology, College of Agriculture, University of Agricultural Sciences, Dharwad, Karnataka, India

S.A. Belorkar     Department of Microbiology and Bioinformatics, Atal Bihari Vajpayee University, Bilaspur, India

Piero Attilio Bianco     Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy (DISAA), University of Milan, Milano, Italy

S. Brindhadevi     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

Paola Casati     Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy (DISAA), University of Milan, Milano, Italy

Raju Krishna Chalannavar     Department of Applied Botany, Mangalore University, Mangalagangotri, Karnataka, India

Jishuang Chen

Bioresource Institute for Healthy Utilization and Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi

College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China

K.S. Divya     Department of Microbiology, Yuvaraja's College, University of Mysore, Mysore, Karnataka, India

Subrata Dutta     Department of Plant Pathology, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, Nadia, West Bengal, India

Jinggui Fang     College of Horticulture, Nanjing Agricultural University, Nanjing, P.R. China

N. Geetha     Nanobiotechnology Laboratory, DOS in Biotechnology, University of Mysore, Mysore, Karnataka, India

Ankit Kumar Ghorai     Department of Plant Pathology, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, Nadia, West Bengal, India

Swapan Kumar Ghosh     Molecular Mycopathology Laboratory, Biocontrol Unit, PG Department of Botany, Ramakrishna Mission Vivekananda Centenary College (Autonomous), Kolkata, India

C. Gourav     Centre for Rural Development and Technology, Indian Institute of Technology Delhi, New Delhi, India

H.G. Gowtham     Centre for Rural Development and Technology, Indian Institute of Technology Delhi, New Delhi, India

Muhammad Salman Haider     College of Horticulture, Nanjing Agricultural University, Nanjing, P.R. China

Tran Thi Minh Hang     Department of Horticulture and Landscaping, Faculty of Agronomy, Vietnam National University of Agriculture, Hanoi, Vietnam

P. Hariprasad     Centre for Rural Development and Technology, Indian Institute of Technology Delhi, New Delhi, India

Vu Quynh Hoa     Department of Horticulture and Landscaping, Faculty of Agronomy, Vietnam National University of Agriculture, Hanoi, Vietnam

S.K. Jadhav     School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India

Archana Jain

Bioresource Institute for Healthy Utilization and Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China

Department of Microbiology, Sri Satya Sai University of Technology and Medical Sciences, Sehore, Madhya Pradesh, India

Subhendu Jash     Department of Plant Pathology, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, Nadia, West Bengal, India

Muhammad Jafar Jaskani     Institute of Horticultural Sciences, University of Agriculture, Faisalabad, Pakistan

Sudisha Jogaiah     Laboratory of Plant Healthcare and Diagnostics, P.G. Department of Biotechnology and Microbiology, Karnatak University, Dharwad, Karnataka, India

I. Johnson     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

Neelu Joshi     School of Biotechnology & Bioinformatics, D.Y. Patil Deemed To Be University, Navi Mumbai, Maharashtra, India

Veenu Joshi     Center for Basic Sciences, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India

G. Karthikeyan     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu, India

M. Karthikeyan     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

Manzoor R. Khan     Section of Plant Pathology, Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

S.M. Paul Khurana     Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, India

Anil Kumar     Department of Plant Pathology, CCS HAU, Hisar, Haryana, India

Narendra Kumar     Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, India

Vipul Kumar     School of Agriculture, Lovely Professional University, Phagwara, Punjab, India

Belur Satyan Kumudini     Department of Biotechnology, School of Sciences (Block 1), JAIN (Deemed-to-be University), Bengaluru, Karnataka, India

Mahantesh Kurjogi     Green Nanotechnology Laboratory, University of Agricultural Sciences, Dharwad, Karnataka, India

Giuliana Maddalena     Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy (DISAA), University of Milan, Milano, Italy

K. Mahendra     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

T. Marimuthu     World Noni Research Centre, Chennai, India

S. Mahadeva Murthy     Department of Microbiology, Yuvaraja's College, University of Mysore, Mysore, Karnataka, India

Muntazir Mushtaq     School of Biotechnology, Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, Jammu, Jammu and Kashmir, India

S. Nakkeeran     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

B. Nandini     Nanobiotechnology Laboratory, DOS in Biotechnology, University of Mysore, Mysore, Karnataka, India

K. Narasimha Murthy     Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India

Atanu Panja     Molecular Mycopathology Laboratory, Biocontrol Unit, PG Department of Botany, Ramakrishna Mission Vivekananda Centenary College (Autonomous), Kolkata, India

Ghazala Parveen     Section of Plant Pathology, Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Alessandro Passera     Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy (DISAA), University of Milan, Milano, Italy

Savita Veeranagouda Patil     Department of Biotechnology, School of Sciences (Block 1), JAIN (Deemed-to-be University), Bengaluru, Karnataka, India

Rakesh Patsa     Department of Plant Pathology, Bidhan Chandra Krishi Viswavidyalaya, Mohanpur, Nadia, West Bengal, India

H.V. Pavan     Department of Microbiology, Yuvaraja's College, University of Mysore, Mysore, Karnataka, India

Hilal Ahmad Pir     Division of Plant Breeding and Genetics, Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, Jammu, Jammu and Kashmir, India

K. Prabakar     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu, India

Fabio Quaglino     Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy (DISAA), University of Milan, Milano, Italy

T. Raguchander     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu, India

Kushal Raj     Department of Plant Pathology, CCS HAU, Hisar, Haryana, India

S. Rajamanickam     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

V. Rajasreelatha     Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, India

L. Rajendran     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu, India

Younes M. Rashad     Plant Protection and Biomolecular Diagnosis Department, Arid Lands Cultivation Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt

Ruby Rawal     Kurukshetra University Kurukshetra (KUK), Thanesar, Haryana, India

P. Renukadevi     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, India

Richa Salwan     College of Horticulture and Forestry, Dr YS Parmar University of Horticulture & Forestry, Hamirpur, Himachal Pradesh, India

Surendra Sarsaiya

Bioresource Institute for Healthy Utilization and Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China

Department of Microbiology, Sri Satya Sai University of Technology and Medical Sciences, Sehore, Madhya Pradesh, India

Santanu Sasidharan     Department of Biotechnology, National Institute of Technology, Warangal, Telangana, India

Prakash Saudagar     Department of Biotechnology, National Institute of Technology, Warangal, Telangana, India

V.P. Savalgi     Department of Agricultural Microbiology, College of Agriculture, University of Agricultural Sciences, Dharwad, Karnataka, India

V. Sendhilvel     Department of Plant Pathology, Centre for Plant Protection Studies, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu, India

Vivek Sharma     University Centre for Research and Development, Chandigarh University, Mohali, Punjab, India

Jingshan Shi     Bioresource Institute for Healthy Utilization and Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China

S.D. Shruthi     Microbiology and Molecular Biology Lab, BioEdge Solutions, Bangalore, Karnataka, India

Monika Sood     School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India

K. Soumya     Field Marshal K M Cariappa College, Constituent College of Mangalore University, Madikeri, Karnataka, India

C. Srinivas     Department of Microbiology and Biotechnology, Jnanabharathi Campus, Bangalore University, Bangalore, Karnataka, India

M. Thippeswamy     Department of Botany, Davangere University, Davanagere, Karnataka, India

Silvia Laura Toffolatti     Department of Agricultural and Environmental Sciences—Production, Landscape, Agroenergy (DISAA), University of Milan, Milano, Italy

Palistha Tuladhar     Department of Biotechnology, National Institute of Technology, Warangal, Telangana, India

A.C. Udayashankar     Department of Studies in Biotechnology, University of Mysore, Mysore, Karnataka, India

S.L. Varsha     P.G. Department of Studies in Microbiology and Biotechnology, Karnatak University, Dharwad, Karnataka, India

A.B. Vedamurthy     P.G. Department of Studies in Microbiology and Biotechnology, Karnatak University, Dharwad, Karnataka, India

Amber Vyas     University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh, India

Shabir Hussain Wani     Mountain Research Centre for Field Crops, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Khudwani Anantnag, Jammu and Kashmir, India

Leela Wati     Department of Microbiology, CCS HAU, Hisar, Haryana, India

Vu Hai Yen     Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Abbu Zaid     Plant Physiology and Biochemistry Section, Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

About the editor

Dr. Sudisha Jogaiah is assistant professor and program coordinator, Laboratory of Plant Healthcare and Diagnostics, PG Department of Biotechnology and Microbiology, Karnataka University, Dharwad. The technological quality and expertise of Dr. Jogaiah’s lab is reflected in an extensive track record of publications with more than 81 peer-reviewed papers, one national patent, and five review articles with an H-index of 23. Also, he has contributed 18 book chapters in various book editions published by Springer, Wiley-Blackwell, and Elsevier. He had also edited three books on bioactive molecules involved in plant-microbe interactions and defense from Springer, Germany, and Elsevier Publications, UK. He is the recipient of Fellow of National Academy of Biological Sciences (FNABS) and has been rewarded with 15 and three international awards. He is editor of Scientific Reports, Plos One, BMC Plant Biology, Frontiers in Plant Science, Annals of Crop Sciences and Agriculture, Journal of Mycology and Plant Pathology, and BioMed Research International.

Foreword

P.K. Chakrabarty, Agricultural Scientists Recruitment Board, Department of Agricultural Research & Education, Ministry of Agriculture & Farmers' Welfare, Govt. of India, Pusa, New Delhi, India

Induction of host plant resistance against a variety of phytopathogens constitutes an advanced strategy of safe and effective plant disease management. Microbial agents have been extensively used quite often for enhancing the tolerance of host plants against a broad spectrum of phytopathogens, through elicitation of systemic acquired resistance or enhanced plant growth and also through active inhibition of plant pathogens. The former class of microbes are more suitably categorized as biostimulants, while the latter group of microbes are referred to as biopesticides. The two categories of microbes in future are expected to be regulated under two different acts, i.e., Fertilizer Control Order 1983 and Pesticides Management Act (presently Insecticides Act 1968). Biological agents (both biostimulants and biopesticides), however, should be integrated suitably as components of IPM with other control measures because various methods are effective at different situations and durations under varying conditions. In recent years, the contribution of biological pest control in sustainable agriculture has been increasing because of its eco-friendly nature and mechanism of action. Biocontrol agents act through mycoparasitism and/or hyperparasitism, antibiosis, competition, secondary metabolites or by inducing systemic resistance and upregulating defense responsive enzymes. Also, plants produce a large array of bioactive compounds, specialized secondary metabolites to defend themselves when facing biotic and abiotic stress conditions. Secondary metabolites play an important role in the way plants interact with their environment and are usually produced in select cell types within the plant. These compounds play an active role in defense against herbivores, fungi, bacteria, viruses, and other plants competing for resources. In spite of the fact that voluminous work has already been published, identification of new potential strains of biological control agents and plant secondary metabolites needs to be characterized and evaluated for their suitability in different climatic conditions and also their effects on various crop plants are yet to be explored.

I am pleased that the book entitled Biocontrol Agents and Secondary Metabolites: Applications and Immunization for Plant Growth and Protection published by Elsevier, UK, provides an up-to-date information of the newer biocontrol agents such as plant inducers and helps to understand the mechanism of biosynthesis of plant secondary metabolites for boosting immunity of plants against biotic or abiotic stresses and discusses its further application in improving crop productivity. Various aspects of biocontrol phenomenon in the book is presented through 29 chapters that have been contributed by eminent researchers who possess in-depth understanding, proficiency, and expertise on the subject at an international level. The authors have systematically organized various information about the potential microbial agents, their biocontrol and biostimulant actions displayed through competitive inhibitory or antagonistic actions as well as through induced host resistance including genomic and metabolomic approaches, in individual chapters. Overall, the book presents cutting-edge developments in the area of biocontrol agents, secondary metabolites they secrete, and their applications in immunization and plant protection, which could serve as a safer alternative to chemicals for the development of sustainable agriculture. Besides, it will also serve as a repository of ideas with many sustainable solutions that could increase the production of safe and healthy food to sustain food and nutritional security of the ever-increasing human population.

I believe that this book will be of immense interest to academia, R&D institutions, policymakers, industrialists, and unemployed youths in complementing small, medium, and even organized enterprises.

Preface

Sudisha Jogaiah

This book aims to bring together the art of findings with their cons and pros of the advances in the field of biocontrol agents and secondary metabolites in agriculture as applications and immunization for plant growth and protection. The chapters covered in this book present interesting cutting-edge developments in the area of sustainable crop improvement. It addresses numerous latest themes covering safer alternative strategies to chemicals for the development of sustainable agriculture, which are described from the latest peer-reviewed literature as reported by eminent researchers who have in-depth understanding, proficiency, vision, and have shown exceptional attributes in their scientific career at the international level. The following are the general overview of the book:

•Discusses the recent development in the practice and integration of biocontrol agents such as plant growth promoters and agrochemicals.

•Outlines the network of biocontrol agents-plants-pathogens mediated through multiple mechanisms for sustainable plant protection.

•Identifies the key challenges on the biopriming of seeds with beneficial microorganisms for enhancing growth and development of plants by regulating several biochemical and physiological processes.

•Compiles the issues that need to be addressed to conserve and to claim the IPR rights of the microbial wealth to retain soil and/or plant health.

•Includes plant secondary metabolites as the key constitutive components of plant defense against various biotic and abiotic stresses.

•Covers biosafety, regulatory requirements, marketing strategy, and exploitation of native biocontrol agents (BCAs) with the concomitant practice of their commercialization globally.

Acknowledgments

I wholeheartedly thank all the authors who have meticulously contributed to advance developments and delivered their views in consideration of both the benefits and the risks on the implementation of biocontrol agents in agriculture for safer and high yielding crops. Thanks are also due to the Karnataka University administration, Dharwad for their support. Also, thanks to Elsevier for taking up the publication of this book. I am also grateful to Dr. P. K. Chakrabarty, Member—Agricultural Scientists Recruitment Board, Government of India, New Delhi, India for his kind words in the foreword.

Introduction

Sudisha Jogaiah

Plants and fungi represent a vast pool of bioactive compounds and are more than ever a strategic source for new and successful commercial products. Recent advances made in genomics, proteomics, and combinatorial chemistry show that nature maintains compounds that have already the essence of bioactivity or function within the host and in the environment. This book intends to cover established and updated research on emerging trends in plant defense signaling in/during stress and growth at the interface of sustainable way of life, in the bifold context of human welfare and conservation of fungi as a group of organisms. Broadly the research endeavors are around the following themes, when a thrust is identified for bioactive molecules in plant signaling for defense. Finally, we provide a perspective on future directions for research in this field that could help in contributing to sustainable crop improvement with higher yields. It is believed that the book will be helpful to postgraduate and doctoral students of molecular plant Pathologists, and to botanists, microbiologists, ecologists, plant pathologists, physiologists, agronomists, molecular biologists, and entrepreneurial mycologists.

1: Fungi endophytes for biofactory of secondary metabolites: Genomics and metabolism

Surendra Sarsaiyaa,c; Archana Jaina,c; Jingshan Shia; Jishuang Chena,b    a Bioresource Institute for Healthy Utilization and Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China

b College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China

c Department of Microbiology, Sri Satya Sai University of Technology and Medical Sciences, Sehore, Madhya Pradesh, India

Abstract

Natural products formed by fungi characterize the chief treasure basis of bioactive molecules. The expansion of metabolism and genomics techniques have prominently contributed to the resurgence of novel metabolite detection, increasing our consideration of multifaceted mechanisms regulating the appearance of biosynthetic gene groups encoding secondary metabolites (SMs). Endophytes, a wide-ranging cluster of microbes having the possibility to chemically bond the gap amongst host plants and microbes, have received the greatest consideration on account of their relatively complex metabolic adaptability. The SMs biosynthesis and their biological functions have not been fully identified in the present time. In this framework, this chapter attracted the recent development in the practice and integration of Genomics with Metabolism approaches with emphases on genomics, proteomics, transcriptomics, metabolomics, metaomics with collective omics as a powerful approach to discover novel metabolite compounds that could support in the large-scale biosynthesis of industrially imperative molecules.

Keywords

Secondary metabolites; Genomics; Metabolism; Fungi; Cluster genes; Biosynthesis

Acknowledgments

The authors are grateful for the financial support under Distinguished High-Level Talents Research Grant from a Guizhou Science and Technology Corporation Platform Talents Fund (Grant No.: [2017]5733-001 and CK-1130-002) and Zunyi Medical University, Zunyi, China for their advanced research facilities. We are also thankful to our key laboratory colleagues and research staff members for their constructive advice and help.

1.1: Introduction

Development has yielded an enormous variety of life span on Earth, trapped in a multifaceted system of dealings and determined by interspecies rivalry for limited ordinary resources. From the organic point of assessment, these associations are regularly mediated by expendable biomolecules, specifically secondary metabolites (SMs), which reflect extant and inexistent connections across progression. SMs are an important resource for the expansion of drugs that contain a heterogeneous type of low-molecular-weight compounds (Leitão and Enguita, 2014). Fungi signify a multipart set of organisms that diversify from unicellular to multicellular complex things, with a wide change of variations that permit the organisms to accept dissimilar existences successfully from saprophytes to herbs, animals to human pathogens, and from symbionts to parasites (Araujo and Maia, 2018). Several species, for example, Aspergillus fumigatus and Aspergillus flavus, are of specific concentration as a consequence of their pathogenicity as a result of both intrusiveness in immunocompromised patients and the toxic complexes they yield, for instance, gliotoxin and aflatoxin. These complexes are often the product of the SMs paths in these fungi. SMs paths offer a number of organic molecules and can also occasionally be medicinally valuable, for example, most excellently penicillin-G, cyclosporine-A, and lovastatin. Subsequently, numerous biosynthetic paths existing in the genomes of fungi form have not been connected to their artifact; this offers a prospect for encounter as additional genomes are sequenced (van Dijk and Wang, 2016).

In the environment, herbs associate with a variation of root-related fungi, which range from advantageous to detrimental. Many fungi have been stated to endorse plant development under, for example, nutrient-deficient conditions, which allows plants to deal with stressful situations (Jogaiah et al., 2013). Arbuscular mycorrhizal fungi (AMF), which are obligate biotrophs, have been considered as valuable. AMF have their place in the fungal group Glomeromycotina, which encompasses the best categorized mutualistic fungi indorsing plant development under nutrient-lacking conditions by transporting nutrients, for example, phosphorus, to its herb hosts. Molecular complexes fundamental symbiosis amongst AMF and 80%–90% of all terrestrial plants are supposed to be progression conserved. This symbiosis association started before 450 million years (Mya), when vegetations started to cultivate on land, as long as there was vital support for addition of plants to nutrient-lacking soil matters (Hiruma et al., 2018).

Plants are conventionally used as drugs and endure to be the basis of plant chemicals with therapeutic assets. These plants chemicals have been used and found to be advantageous to humans. Microorganisms, for example, fungi, bacteria, and to a lesser range viruses, that attack and reside inside the plant’s tissues are the so-called endophytes, which accurately resource within plants. The symbiotic association is known as mutualistic relationship when the microorganism (endosymbiont) with the host plant can share benefit to each other, while a commensalism relationship is indicated that the endosymbiont can be live inside the host without disturbing it. Fungal endophytes may exist within the host roots, leaves, or stem of the plant and incline to replicate just previously or during the senescence point of the plant as a result of which time the reproductive structure would be out. These plant endophytes often yield compounds that may be damaging or valuable to the plant, and accordingly may be taken out for their therapeutic rate or may be of agrarian value (Daley et al., 2017).

Today, we distinguish that even though most existing organisms can yield SMs, the capability to yield them is unequally dispersed (Nakkeeran et al., 2019). Amongst all recognized microbial antibiotics and comparable bioactive complexes (in total 22,500), 45% are of actinomycetes, 38% are of fungi, and 17% are of unicellular bacteria. Amongst this treasure of compounds, only about a hundred are in real use for human remedy, with the mainstream being resultant from actinomycetes. Nevertheless, it is worth revealing that in addition to penicillin, numerous other fungal SMs have positively reached the pharmacological marketplace, together through cholesterol disenchanted statins, the mycophenolic acid with immunosuppressant, and the antifungal griseofulvin (Nielsen and Nielsen, 2017).

Biosynthesis of SMs takes place from an imperfect figure of precursor metabolites from the chief metabolism. In fungi, some precursors are mostly short chain (SC) carboxylic acids (e.g., acetyl coenzyme A) or amino acids, which are allied by a backbone catalyst, for example, of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), dimethylallyl tryptophan synthetase (DMATS), and/or terpene cyclase (TC). The subsequent oligomers are then focused on chemical alteration by tailoring enzymes which are frequently measured under a shared transcriptional parameter as the backbone enzyme. A hallmark trait of the genes complicated in an SMs pathway is that they, in the greatest cases, actual cluster in the chromosome in BGCs (biosynthetic gene clusters) (Nielsen and Nielsen, 2017).

Fungal metabolites and its action mechanisms could trigger the bio-mechanism approaches for enhancing crop development with its protection. Although the available research data (nature and function of secreted microbial metabolites) of endophytic fungi are identified predominantly, which are unbalanced in plant microbial interactions. Both fungi and bacteria yield diverse instable (or semivolatile) organic compounds (OCs), which include multiple courses of short molecular form lipophilic metabolites and their byproducts that evaporate at typical pressures and temperatures (Li et al., 2016).

Fungal SMs biosynthesis pathways are included core enzymes, which are considered as a compound backbone. Finding of novel SM genes is frequently proficient by homology explorations using identified genes of these principal enzymes. Expediently, in several cases, the supplementary genes (coding for adapting enzymes, transcription factors, resistance proteins, or transporters) in the biosynthetic route are grouped in the genome; thus, they can be recognized easily as soon as the core enzymes have been recognized. There are plentiful ways to connect the identified SM pathways with their products (van Dijk and Wang, 2016). The typical collecting genes besides the preserved motifs of mainstay genes can be oppressed for computational finding of BGCs from sequence figures. Tools like antiSMASH, SMURF, PRISM, and CASSIS/SMIPS employ these structures to dependably and with high correctness distinguish BGCs of the identified compound in endophytic fungi. Additional algorithms distinguish BGCs deprived of relying on exact motifs or the attendance of backbone genes, which allows BGCs identification beyond PKS, DMATS, NRPS, and TCs. Tools and executions of mining algorithms of BGC have been broadly reviewed (Nielsen and Nielsen, 2017).

Employing metabolic engineering to evade these limits can be greatly supported by operation of the scientific depiction of genome-scale metabolism in metabolic models, whose perceptions and applications have been reread in a different part. These models, though, often neglect SM biosynthesis, and hence their probability in studying SM has not been entirely selected. Furthermore, with the well-organized gene editing implement CRISPR Cas9 being advanced for a sum of fungal protoorganisms, a countless potential occurs for implementing the compulsory genetic alterations for the progress of improved SM producers (Nielsen and Nielsen, 2017).

1.2: Fungal endophytes frequency and transmission in plant organizations

Endophytes are frequently transmitted to the plant host vertically, specifically from generation to the next group over nonsexual propagation or spores, perhaps seen through the Neotyphodium spp. These endophytic are typically germ-free, though a few fungi, similar to Epichloe spp., are adept at acclimatizing to the environmental alteration and replicating sexually liberating spores that will certainly contaminate a neighboring host plant. Alternatively, during horizontal communication, these endophytes yield spores via asexual or sexual replica for insect and breeze dispersion. An endophyte may also be shifted straight through revelation to an adjacent infected herb. These endophytes at that time reproduce subsequently in either advantageous or deadly effects (Daley et al., 2017).

1.3: Endophytic fungus as biofactory of bioactive compounds

SMs are unique bioactive molecules formed by various organisms together with bacteria, floras, and fungi (Jogaiah et al., 2016). These compounds (as bioactive molecules) are predominantly ample in soil-residing fungi, which occur as multicellular groups competing by means of minerals, nutrients, and water (Keller et al., 2005). Contrasting primary metabolites, maximum SMs—as their term advocates—are not important for fungal development, progress, or replica under in vitro environments. They can, though, provide a shield in contradiction of various environmental pressures and throughout antagonistic communications with added soil populations or a eukaryotic mass. At a similar period, fungi are also recognized to produce plentiful mycotoxins, for example, aflatoxin, trichothecene, fumonisin, and zearalone (Khaldi et al., 2010).

1.4: Genome level secondary metabolism metabolic modeling

Several SM clusters were categorized at the molecule level together with the gliotoxin (Gardiner and Howlett, 2005), fumitremorgin, fumigaclavines (Unsold and Li, 2006), and siderophores biosynthesis clusters. The sequencing of the entire genome also discovered that the number of SMs characterized from a certain strain falls far in arrears of the clusters numbers that can be predicted based on its gene sequence figures (Chiang et al., 2008a,b). This has been accredited to the fact that not many clusters may be articulated under typical laboratory environments. Notwithstanding the agricultural and medical status of fungal SMs, maximum SM putative clusters in endophytes genomes have been foreseen by ad hoc approaches based on guide reviews of BLAST explorations created for genes backbone and their neighbors. A manual footnote of SM clusters, though, is time intense and may result in unpredictable annotation (Khaldi et al., 2010).

1.5: Gene clusters for fungal metabolism: Diversity and distribution

Gene clusters for fungal metabolism (GCFM) are loci that encompass multiple genes from diverse gene groups, which offer support to a disconnected metabolic phenotype. Currently, maximum metabolic phenotypes have been found to be programmed by GCFM contribution in nutrient acquisition, or the degradation/biosynthesis of SMs, amino acids, and cofactors. The initial GCFM was to be identified in the strain of Saccharomyces cerevisiae galactose consumption cluster (GAL). Ensuing nutrient acquisition GCFM discoveries contain the catabolism of quinic acid cluster in Neurospora crassa (QA), the catabolism of proline (PRO), and the assimilation of nitrate (HANT) clusters in Aspergillus nidulans, all of which revealed an extensive in-depth investigation previously to the age of comprehensive-genome sequencing. The evolutionary and functional mechanisms of the bio-synthetic genes are clustered quickly for the development and protection of the plants (Walton, 2000). More newly, nutrient operation clusters have been recognized in fractional and broad genome sequences over a manual explanation of gene purposes and by fungal analogues identification via bacterial operons (Jeffries and van Vleet, 2009). These include GCFM complex in sugars utilization (e.g., rhamnose and N-acetylglucosamine), catabolism of amino acid, and iron metabolism.

GCFM are also intricate in basic intracellular metabolism through contributing in the synthesis of a numeral of amino acids, vitamins, and other vital metabolites. All vitamins may be supposed to be as inimitable or complex metabolites, which cover essential metabolic ways to focus on minute numbers, but that are frequently acquired slightly than made endogenously. Likewise, rare but vital amino acids may be assimilated from other microorganisms or synthesized. Numerous pathways for amino acid/vitamin synthesis are associated by the inclination of the genes for their cluster metabolism in both prokaryotes and fungi (occasionally). Though the maximum vitamin biosynthetic routes have been adeptly clustered in bacteria, only a combine of fungal vitamin clusters have been recognized, counting the biotin cluster (Hall and Dietrich, 2007) and the functionally measured pyridoxine group in Saccharomyces to date (Li et al., 2016). Clustering is not entirely a functional, optional, or niche-specific pathway, however, even though that is undoubtedly the greater inclination. The AROM synthesis pathway of amino acids (aromatic) is the most commonly well-kept-up pathway amongst fungi. AROM was initially supposed to be an operon or gene cluster in fungi comparable to that in bacteria, but was later start to be a penta-property peptide that resulted from the integration of monofunctional inherited genes (Giles, 1978).

It is tough to conclude whether ecological tendencies occur in gene clustering, for the reason that fungi incline to be opportunistic and acclimatize to ecological parts rapidly. Though, the widespread gene is clustered in class of Eurotiomycetes, which is present equally in the Aspergillus spp. (de Vries et al., 2017) and several others microcolonial black yeasts (Teixeira et al., 2017). These are recommended GCFM in the soil saprotrophs. With the finding of novel fungal genome data and enhancements in GCFM detection algorithms, prospects to study wider outlines of fungal SM GCFM diversity are better than they have constantly been. Currently, the genomics of fungi has described the phylogenetic diversity at complex levels or within the species or genera (de Vries et al., 2017; Teixeira et al., 2017). Future exertions to sample genomes intensely within defined fungal groups will provide better power to conclude direct relations between GCFM encoded purposes and fungal biology (Slot, 2017).

Associated with other strictly connected Aspergillus species, Penicillium and P. digitatum produce lesser SMs with identified products, for example, phenylalanine-proline diketopiperazine and tryptoquialanines (TQA). The obtainability of the fungus’s genome arrangement also enables the investigation of SM product outlines of P. digitatum by means of SM biosynthetic gene groups of genome mining (Sun et al., 2013). This study associated the transcriptomes of P. digitatum cultured in chemical medium and recovered from decomposed citrus fruit, and initiated four upcontrolled genes in enriched biosynthetic gene clusters. A wide-ranging annotation of four biosynthetic gene clusters was then made with the hybrid usage of the domain account, RNA-sequence gene expression, and genomic synteny, which recognized three SM biosynthetic paths (SMBP1–3). Amongst closely connected strains, SM biosynthesis connected gene clusters specific for biosynthesis are commonly detected between well-preserved genomic areas, for example, the clusters (gsf and vrt) in P. aethiopicum (Chooi et al., 2010), and disruptions in synteny typically indicate gene cluster limitations (Inglis et al., 2013), which may be owing to the function of horizontal gene transmission in gene clusters (Campbell et al., 2012). SMBP1–3 is also observed between well-maintained genomic areas and their mechanisms are controlled in a similar way. SMBP2 is the exact tqa cluster in the comparative genomics, particularly synteny analyses. It will help to the accurate annotation of gene clusters (Zhu et al., 2017).

In view of the large amount and ubiquity of polyketides (aromatic) in nature, moderately few of their biosynthetic paths have been explained (Griffiths et al., 2016) Amongst the finest known are the paths of the emodin-derivative monodictyphenone as well as the carcinogenic aflatoxin in some Aspergillus strains (Yu et al., 2004). The main enzymes in the fungal biosynthesis aromatic polyketides are polyketide synthases, great multidomain schemes (type I) that extend its polyketide products (Crawford and Townsend, 2010). The assemblage of modest carboxylic acid structure blocks to a polyketide (aromatic) is attained by a series of three core areas: an ACP: Acyl-carrier protein that helps as a chain of the mounting polyketide, a malonyl CoA-ACP transacylase that chooses and allocates the extender part malonyl-CoA and a ketosynthase (KS) which catalyzes recurrent decarboxylative strengthening in directive to consecutively extend the polyketide support. Typically, a thioesterase (TE) field forms the catalyst C-terminus, cyclizes, and releases the end product. A unique characteristic of the fungal PKSs aromatic is the nonappearance of any reductive area, which is why they are referred to as NR-PKSs (nonreductive PKSs). Additionally, NR-PKSs comprise two other unique areas: the starter unit: ACP transacylase that chooses the (typically nonmalonyl) appetizer unit (Crawford et al., 2006) and the product pattern (PT-) domain that arbitrates the regioselective cyclization of the extremely sensitive poly-β-keto intermediates and orders the final construction of the produce (Jahn et al., 2017).

Some of the key databases have shown a very great variety of experimentally consideration such as IMGABC, ClusterMine360, and MIBiG. Separately from the sequence data and catalytic domain association, the major usefulness of these databases is to find the chemical buildings of the secondary metabolite. A recent type of ClusterMine360 has evidence on almost 290 gene clusters complicated in biosynthesis of over 200 nonribosomal peptides and polyketides. In accumulation of a genes sequence, catalytic domain group, and chemical assembly of a secondary metabolite end product, IMG-ABC30 has also catalogued data on genomics locus for a huge number of SM gene clusters. The MIBiG31 database has been established for determine the SM biosynthetic paths information while MIBiG-submissive reannotation has been used for SM biosynthetic gene clusters. An alternative example of a valuable database for SM is NORINE, which has many chemical forms for 1168 nonribosomal peptides. On the basis of bioinformatics investigation of experimentally considered NRPS and PKS gene clusters, a numeral of computational approaches has been technologically advanced for joining metabolites genes. Taking into consideration the notable conservation of a total biosynthetic model for nonribosomal peptides and polyketides, these computational approaches have fundamentally used a knowledge-grounded approach for deriving forecast rules founded on experimentally considered NRPS and PKS gene clusters (Khater et al., 2016).

The apparatuses like NRPS-PKS, SBSPKS, ASMPKS/MAPSI, ClustScan, NP.Searcher, NRPSpredictor, PKS/NRPS, and PKMiner permit semireflex identification and explanation of PKS, NRPS, or PKS-NRPS hybrid gene clusters. Along with annotating the areas of multidomain NRPS and PKS, many of these tackles also forecast the acyltransferase (AT) and adenylation domains substrate specificity. Apart from identification of dissimilar catalytic areas of PKS and NRPS, SBSPKS can be perfect three-dimensional constructions of comprehensive PKS modules and foresee the directive of substrate channeling in the event of PKS clusters containing numerous ORFs. Bioinformatics tools have as well been developed for examination of a specific type of SM gene clusters. SMURF43 permits identification of gene clusters in a fungal genome for biosynthesis, even though PKMiner42 supports in mining of gene clusters category II PKS. Bioinformatics tools for examination of SM biosynthetic genes have also been established for the study of metagenomic information (Khater et al., 2016).

Metagenomic models can be rapidly scanned for different natural products by PCR primers precise for SM biosynthetic gene groups. This PCR-built sequence tag method has been joined with in silico genomic tools to examine for putative SMs. eSNaPD has been specifically advanced to analyze bulky meta genomic arrangement tag datasets and support in the detection of diverse secondary metabolite clusters. Another bioinformatics which admits sequence identifiers from metagenomic data lengthwise with protein and genomic sequences is NaPDoS. It uses genomic information to explore and categorize NRPS Adenylation and/or PKS Ketosynthase domains (Khater et al., 2016).

The recently established antiSMASH47 channel can recognize the biosynthetic loci cover the entire range of identified SM compound classes (nonribosomal peptides, polyketides, terpenes, aminocoumarins, indolocarbazoles, aminoglycosides, bacteriocins, nucleosides, lantibiotics, beta-lactams, siderophores, melanins, butyrolactones, and others). antiSMASH48 is also combined with other tools corresponding to ClusterFinder49 which permits identification of putative SM gene clusters programming a novel type of SM. It is used for the PFAM domain 50 to examine the enzymes present in the biosynthesis of SM. It also permits a comparison of recognized clusters with experimentally considered clusters via cluster BLAST. The latest information of antiSMASH can recognize active site deposits of core PKS areas like KS, AT, DH, ACP, KR, TE and tailoring areas like cytochrome P450 oxygenase by means of the Active Site Finder segment. antiSMASH also uses the domain info of linked NRPS and PKS to foresee the linear polyketides shaped by the enquiry cluster. Though the chemical construction prediction feature comprises a consequence of reductive areas DH, KR, and ER on the polyketide construction, forecasts of post-PKS/NRPS variations and cyclizations are not yet obtainable in antiSMASH (Khater et al., 2016) (Fig. 1.1).

Fig. 1.1 Conventional and modern approaches for microbial metabolites.

1.6: Methodological and technological advancement of genome for metabolites

1.6.1: Strategies for targeted genome editing

The SM genome editing is the alteration of a predetermined locus inside a genome with the specific region. Genome editing approaches must have the precondition of producing genetically constant organisms, be informal to use in contradiction of a series of DNA arrangements, and preferably must be also informal to perform in an extensive range of organisms (Kim and Kim, 2014). Targeted genomic alterations are built on the insertion or deletion of genetic evidence, and are strongly reliant on genetic recombination. Classical methods used for genome excision are built on homologous recombination, a procedure with an enormously low efficiency, particularly in higher eukaryotes which stalled its routine application. However, several resolutions have been established to increase the competence of genetic recombination, together with the use of tenable and directed nucleases. This enzyme family is used to breakdowns DNA double-strand at specific positions within the genome, and also activated the nonhomologous inference joining development (Boettcher and McManus, 2015). The double-strand breakdowns generation at precise DNA loci can be also utilized to simplify homologous recombination to supplement DNA fragments and produce recombinant strains. There are two main programmable nucleases family, a protein-directed nuclease, composed by Zn-finger in addition to transcription activator-comparable effector nucleases, with a nucleic acid-guided nuclease intimate, mainly signified by the CRISPR-Cas9 scheme (Leitão et al., 2017).

1.6.2: Protein-directed nucleases

The primary programmable nucleases were technologically advanced at the close of the 1990s as designed by the restriction enzyme to cut at all DNA in a preresolute arrangement. Zinc-finger domains were concocted by a plan based on a modular assemblage of adapted DNA binding areas, each of which distinguishes an exact three base pair arrangement within the DNA, to produce a set of 64 unlike domains able to identify any desired DNA arrangement when collective in the proper direction (Leitão et al., 2017; Segal et al., 2003).

1.6.3: Nucleic acid-guided nucleases

A third cluster of the genomes editing way is established by the RNA-directed nucleases characterized by the CRISPR-Cas9 scheme. The extensively recommended CRISPR-Cas9 genome editing scheme is a minimalist type derived from a primeval bacterial immune scheme that regulates the operative response in contradiction of bacteriophage contaminations isolated from the Gram-positive Streptococcus pyogenes bacteria (Barrangou et al., 2007). For effective binding, the ds DNA is cuts by the enzyme Cas9 necessary for the occurrence of the PAM (Protospacer adjacent motif) (Mojica et al., 2009). In an attempt to evade these target assets, a careful strategy of the gRNA arrangement and the usage of specific Cas9 modifications is recommended (Cho et al., 2014). Numerous computer procedures such as Cas-OFFinder, CHOP–CHOP, CCTop, sgRNAcas9, and COSMID were precisely advanced to support in gRNA strategy and off-target prophecy (Leitão et al., 2017).

1.6.4: Further tools for genome editing: Integrases and recombinases

The application of nucleases for the exact insertion of DNA wreckages into a genome is eventually reliant on a recombination response, which is essentially incompetent in eukaryotes. However, the exogenous DNA insertion in precise genomic loci can be improved by the operation of recombinases or integrases. A recombinase-intermediated cassette conversation is a multipurpose genome editing way which exactly substitutes a genomic target holder by a well-matched donor concept by the assistance of specific recombinases. A targeted genome operation by RMCE is stringently dependent on the reality of specific recombination positions (RT or attB) in the designated genome (Rutherford and Van Duyne, 2014). Nucleases such as CRISPR-Cas9 or TALEN can be also applied to present integrase recombination positions in any genome, provided that specific stages for heterologous gene countenance with comprehensive control ended content, course, and copy quantity of implanted genes. As an applied example, this approach has been positively employed in pluripotent stem cells of humans to supplement genes of concentration flanked through attB locations of Bxb1 and phiC31 integrases in a precise locus (Zhu et al., 2014). Further requests of RMCE procedure are predictable in the subsequent years, particularly in the pitch of gene appearance and metabolite production (Leitão et al., 2017).

1.7: Production of SMs by pathway-specific overexpression regulatory genes

Pathway-specific regulatory proteins of fungoid SM gene groups are frequently determined inside or directly together with the specific gene cluster. Characteristically, these proteins regulate the countenance of the complete gene cluster. They are not articulated under cluster noninducing situations. Thus, overexpression of their coding genes is an informal way to trigger the transcription of altogether pathway-precise genes. The benefit of this method is the supervision of only a solitary, relatively minor gene and the opportunity for both a specific and ectopic addition of the overexpression concept. Stimulatingly, the recent data has exposed over expression of a single pathway-precise regulator for the stimulation of SM gene (Bergmann et al., 2010). The fungi alcAp (alcohol dehydrogenase supporter) and gpdAp (glycerinaldehyde-3-phosphate dehydrogenase promoter) supporters were effectively applied to overexpress pathway-precise regulatory genes. As a consequence, novel mixtures were recovered and product produces of known compounds amplified (Chen et al., 2010). A number of supporters are obtainable for the protein’s overexpression in filamentous fungus (Nützmann et al., 2012).

In Trichoderma strain, the numerous genes are responsible for the biosynthetic gene clusters, including core enzymes, for example, NRPSs (nonribosomal peptide synthetases), PKSs (polyketide synthases), or cyclases/terpene synthases, and addition enzymes (like cytochrome P450s, methyl transferases, oxidoreductases, etc.) (Bansal and Mukherjee, 2016a,b; Jogaiah et al., 2018). Six extra genomes (the mycotrophic Trichoderma harzianum, Trichoderma asperellum, Trichoderma parareesei, Trichoderma gamsii, and the devious human pathogens Trichoderma citrinoviride and Trichoderma longibrachiatum) were afterward supplementary to the public records (Zeilinger et al., 2016). The fungal SMs biosynthesis often involves exclusive and uncommon biochemical paths. These may be to some extent wide-ranging to yield a higher substances diversity from only a limited key precursor resultant from primary metabolism (Keller et al., 2005). Trichoderma-resultant SMs encompass nonribosomal peptides, for example, siderophores, diketopiperazines, and peptaibiotics like gliovirin, gliotoxin, polyketides, pyrones, terpenes, and isocyane metabolites (Zeilinger et al., 2016).

Comparable to other fungal strains, the appearance of SM-connected genes in Trichoderma spp. is recognized to be measured by connections with pH signaling, the velvet-intricate proteins, and other (micro)organisms. Atanasova et al. (Atanasova et al., 2013) deliberate the transcriptomic rejoinders of T. atroviride, T. reesei, and T. virens to the occurrence of R. solani. Two PKSs are controlled by the genes present in the R. solani, T. atroviride and R. solani, T. reeseie, while the genes are present in the synthesis group of gliotoxin are uncontrolled in the T. virens. T. atroviride is additional described for the lipoxygenase genetic factor to be complicated in the 6-PP biosynthesis system (Kubicek et al., 2011), while the development of T. arundinaceum in coculturing with B. cinerea has led to improved expression stages of the novel Tri biosynthetic genetic factor (Malmierca et al., 2015).

1.8: Genetic makeup of fungal secondary metabolism

In microbes, it is extensively alleged that SMs are biochemical signaling things synthesized for messaging and performing a chief part in competitors’ self-consciousness (Brakhage and Schroeckh, 2011). The SM biosynthesis coding genes in fungi are also settled in clusters that can extend over 10 kb, while there is a limited exception (Lo et al., 2012). The SM gene's arrangements are restricted in cluster's usage of fermentation practice as a suitable and viable alternative at large-scale production of metabolites (Wu and Chappell, 2008). These clusters typically code for enzymes complex, for example, the NRPS: nonribosomal peptide synthetases, or PKS: polyketide synthases that consist of numerous domains and components with defined purposes (Strieker et al., 2010). These multimodular enzymes display high resemblance in their mechanisms and architecture, intricate in the product assemblage, thus aiding in employment of different matters. To produce the structural support of the particular NRPS, SMs and PKS use malonyl clusters and amino acids and their byproducts as the structure blocks (Brakhage and Schroeckh, 2011). Nonribosomal peptides (NRP) and polyketides (PK) form a support for most of the SMs. Many of the NRP derivatives comprise clinically significant antibiotics, for example, cephalosporin, penicillin, and immune suppressants identical to cyclosporine, while lovastatin results from the polyketide support. Some complexes fall underneath the diverse NRP-PKS hybrid derivation like aspyridones (Bergmann et al., 2007) though some others are comparable to oxylipins (derivatives of fatty acid) with a gibberellins (terpene derivative) consequence from additional paths. In the previous study, the endophytes have received much consideration due to their maximum metabolic adaptability. Many reviews have described the attention of endophytes SMs. While endophytes have been energetically screened for their ability to elicit host-resultant phytochemicals, other information clearly designates that endophytic fungi also form a miscellaneous variety of different SMs (Deepika et al., 2016).

1.9: Identifying gene clusters of fungi

With the accessibility of a growing quantity of fungal genomes, there has been a rapid growth in foreseeing and recognizing putative SM formation genes accountable. Bioinformatic algorithms, perhaps SMURF [SM Unknown Regions Finder] (Khaldi et al., 2010), antiSMASH, and FungiFun, are accessible for gene clusters identification and responsible for SM. These tools support in the genes coding prediction for core NRPS and/or PKS enzymes, laterally with the foreseen function of the together genes to support in identification of SM clusters in the entire genome (Bergmann et al., 2007). These processes have been effectively utilized to recognize approximately 50 gene clusters in fungi, Aspergillus strain (28–40 Mb genome size) and in Arthroderma sp. with 27 gene clusters (22 Mb genome size) (Burmester et al., 2011). Since the efficient structural physiognomies of the metabolites determined by these groups continue to be largely unidentified, these are called orphan or cryptic clusters (Bergmann et al., 2007; Deepika et al., 2016).

1.10: Applications for secondary metabolites through genome editing and metabolic engineering

Efficient genomics is a division of the molecular science established by unit approaches that analyze the active genotype–phenotype relations. In order to regulate the genetic source accountable for an assumed phenotype, onward genetics is the most secondhand classical method in functional genomics. Primarily, forward genetics depends on the random formation of mutants by chemical or radiation mutagens and additional mapping of genomic positions. This way was applied for the explanation of genes intricate in the formation of antibiotics and many supplementary metabolites with medical uses (Lewis, 2013). Currently, advancing genetics functional transmissions can be intended more reasonably, taking the gain of the current increase in obtainable genomic statistics. Furthermore, we can also methodize the practical genomics subsequent viewpoint of the opposite genetics to determine the functional values of a genetic alarm in a specific genomic locus (Shah et al., 2015). Mutually forward with reverse inheritances can benefit from genome excision protocols (Leitão et al., 2017).

1.10.1: Forward genetics applications

Despite the presence of much genome excision information, the CRISPR-Cas9 system is used for the numerous applications. The RNA-guided directing of the Cas9 endonuclease and its alternatives to every genomic locus are found ideal to achieve high-throughput data that could be possibly explored the detection of new SM with biological action or for the regulation of the governing mechanisms leading to the formation of the previously known substances. Libraries of arrayed or pooled gRNAs can be applied together with innate Cas9 or its useful variants to achieve the functional screenings covering a comprehensive genome (Evers et al., 2016). The appearance of Cas9 alternatives in the target cells can be attained by using combined stable cells or bypassing expression arbitrated by transformation by plasmids encrypting Cas9 variants measured by specific supporters. The general approach, advantages and weaknesses, and uses for the useful CRISPR-based transmissions in eukaryotic cells, has been freshly reviewed in a different region (Housden and Perrimon, 2016; Shalem et al., 2015). Expansion of function screenings could be achieved by the usage of protein combinations comprising the inactive dCas9 mutant and an effector protein. The functional effectors, which could relate to the transcription factors family, will be directed to specific genome sections by the bonded dCas9 protein and the consistent gRNA. This approach has been effectively working in human cells with the help of the VP64