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This reference work presents an authoritative review of endophytes and their applications to human welfare. Endophytes have become a class of interesting and curious microorganisms due to their intimate intra- and intercellular association with plants for competence, survival and reproduction. They can be bacteria or fungi, and they are usually non-pathogenic to their host. Endophytes have important applications in agriculture and industry, namely, they can help with plant growth, act as biocontrol agents and biosurfactant and secondary metabolite producers, and they are also rich sources of bioactive natural products.

Novel and beneficial effects of endophytes are constantly emerging, and this book, divided into four sections, provides readers with the latest developments in this fast expanding field. In the first section, readers will discover the biology of the major groups of endophytes, followed by a summary of conventional and molecular tools for endophytes’ identification in Section II. The production of high-value metabolites by endophytes will be explored in the third section of this book, and in the final section, readers will find several case studies, examples and prospects for endophytes’ application in agriculture and industry.

Written by leading international authors, this reference work will appeal to a wide readership, from students and researchers in the field of botany, biotechnology and agriculture to professionals interested in the production and applications of endophytic metabolites.

Inhaltsverzeichnis

Frontmatter

Biology of Major Groups of Endophytes

Frontmatter

1. Biologically Active Compounds from Bacterial Endophytes

Abstract
The phytomicrobiome plays a key role in incrementing the fitness of the host. The interactions between plants and their microbes yield a vast and diverse assortment of secondary metabolites. The myriad of genes within bacterial cells thriving inside plant tissues (i.e., endophytes) contributes to the production and conversion of small molecules into bioactive compounds, and the genome mining can be a powerful tool to extract this knowledge from large amounts of data sets. In this chapter, annotated biosynthetic gene clusters (n = 4614 unique within 60,632 genes) from genomes of endophytes assigned to Actinobacteria (n = 26), Bacteroidetes (n = 6), Firmicutes (n = 15), and Proteobacteria (n = 99) were analyzed and predicted to be involved in the biosynthesis of 4766 types of secondary metabolites classified within 22 families. The vast majority of secondary metabolites was predicted as putative (n = 3684), followed by those involved in the biosynthesis of nonribosomal peptide synthetase (n = 293), polyketide synthases (n = 268), and terpene (n = 120) compounds. This reveals that the community of endophytes conceals a great source of potential proteins with novel enzymatic activities and novel families of secondary metabolites.
Pablo R. Hardoim

2. Endophytic Pseudomonads and Their Metabolites

Abstract
Plant microbiome is crucial in maintaining both plant health and ecosystem functioning. Rapid advance in next-generation sequencing technology has brought about a paradigm shift in our understanding of plant microbiome. This has especially shed light on selective colonization of microbes in root compartments, i.e., rhizosphere, rhizoplane, and endosphere. A growing body of evidence reveals the predominance of the phylum Proteobacteria in endomicrobiome of several crop plants. Additionally, Pseudomonas is found to be a widely distributed genus within Proteobacteria which exists in both above and below ground plant parts. Pseudomonads are extensively exploited for their metabolic potential and adaptability toward endophytic lifestyle in contrast with their rhizospheric counterpart and fungal endophytes. This together develops a better understanding of the genus Pseudomonas as key determinants in plant health including their role as biocontrol agents. In this chapter, we discuss pseudomonads with endomicrobiome perspectives, their atypical characteristics with respect to rhizospheric microbes, and influence of metabolites in context with their role in plant growth and biocontrol. A comprehensive understanding about selection of endophytic lifestyle will perhaps provide better opportunities to improve plant performance and pathogen resistance.
Apekcha Bajpai, Bhavdish N. Johri

3. Diversity, Ecology, and Significance of Fungal Endophytes

Abstract
Fungal mutualistic association with plant species has become one of the important emerging contemporary issues in biology. Non-mycorrhizal endophytic fungal studies have multifold interest owing to their basic and applied value. Various tissues (leaf, stem, bark, seed, root, rhizome, and tuber) of a wide array of phototrophs (forest trees, plantations, shrubs, medicinal plants, vegetables, macrophytes, seaweeds, seagrass, ferns, and orchids) occurring in different ecosystems (terrestrial, riparian, freshwaters, mangroves, marine, marshes, and coastal sand dunes) have attracted the attention of researchers. The main focus of such interest is to understand their coevolution, life history, lifestyle, diversity, ecology, stress tolerance, natural products, biological control, bioprospects, and bioremediation. Climate change and anthropogenic interference on biodiversity have dramatic impact on the mutualistic association between plant species and endophytic fungi. The purpose of this review is to provide a brief overview on endophytic fungal studies carried out in different plant species, ecological perspectives, methods, and applications in different fields.
Kandikere R. Sridhar

4. Bioactive Metabolites from Turkish Marine Invertebrates and Associated Fungi

Abstract
Nature provides a broad arsenal of structurally diverse and pharmacologically active compounds that serve as highly effective drugs with advanced chemical structures for the development of novel synthetic drugs to combat a multitude of diseases. Marine natural products are considered as promising sources of new secondary metabolites with pharmaceutical potential. Turkey has over 8300 km coastline with different geographical zones or habitats accounting for a great amount of diversity among its species. The largely unexplored Turkish seas with a wide range of biological diversity provide a lot of scope in future. In this section, we have tried to assemble studies of Turkish marine invertebrates and associated fungal species attempted so far.
Belma Konuklugil, Hajar Heydari

5. Endophytes of Nothapodytes nimmoniana (J. Graham) Mabb.

Abstract
Endophytes are excellent source of bioactive natural products. Fungal and bacterial endophytes have been isolated from medicinal plant Nothapodytes nimmoniana, and majority of them have the capability of accumulating camptothecin (CPT) similar to host plant. Entrophospora infrequens, Neurospora crassa, Fusarium oxysporum, Colletotrichum fructicola, and Corynespora cassiicola are some of the fungal isolates which have been cultured by following submerged fermentation and solid-state fermentation methods for the production of CPT. Here we presented the detailed account of various endophytes isolated from Nothapodytes nimmoniana and recent research developments made in this area.
Hosakatte Niranjana Murthy, Dayanand Dalawai, So-Young Park, Kee-Yoeup Paek

6. Endophytes of Ginseng

Abstract
Ginseng (Panax ginseng C. A. Meyer) is a well-known medicinal plant which is used as a tonic in oriental medicine. Ginsenosides are the most important secondary metabolites of ginseng which have pharmacological effects including anticancer, antidiabetic, immunomodulatory, neuroprotective, hepatoprotective, and anti-stress properties. Bacterial and fungal endophytes associated with ginseng plants have been isolated, characterized from its natural distribution range. Endophytes of ginseng showed tissue or organ, age, genotype, and geographical location specificity with their distribution and abundance. Bacillus, Burkholderia, Lysinibacillus, Micrococcus, Paenibacillus, and Pseudomonas are major bacterial genera isolated from ginseng. Alternaria, Colletotrichum, Entrophospora, Fusarium, Paecilomyces, Penicillium, Phoma, Setophoma, Verticillium, and Xylaria are the most frequent fungal genera isolated from ginseng. Majority of ginseng endophytes depicted many of biological activities such as plant growth promotion, antimicrobial, antitumor, ginsenoside biosynthesis, and biotransformation activities. In this chapter we presented the recent progress made in the area of biology of ginseng endophytes.
Hosakatte Niranjana Murthy, Dayanand Dalawai, So-Young Park, Kee-Yoeup Paek

7. Endophytism in Zingiberaceae: Elucidation of Beneficial Impact

Abstract
Endophytism is a unique relationship between plant and endosymbiotic microorganism wherein the microbes colonize within plant tissues without producing any disease etiology. Various groups of endophytes isolated from different medicinal plants are extremely significant in this respect for their ability to synthesize novel bioactive compounds as well as for the modulation of productivity. Endophytes also play various crucial roles in growth, biotic and abiotic stress tolerance, and adaptation. With the implementation of “state-of-the-art” technologies in molecular biology, the specific identification of associated microorganism as well as their relationship with corresponding host plants has been explicitly deciphered in recent years. Zingiberaceae, generally recognized as ginger family, comprises of rhizomatous medicinal and aromatic plants and is characterized by the presence of plethora of bioactive compounds along with volatile oils. They are widely cultivated in tropical and subtropical regions of Asia. This chapter aims to explore the endophytic relationship between medicinally important species of Zingiberaceae and the corresponding microbes, for improved production of imminent natural products and their role in protection of host plants from pathogens as well as in stress tolerance, thus helping the plants, indirectly, to grow better.
Avijit Chakraborty, Subrata Kundu, Swapna Mukherjee, Biswajit Ghosh

Biotechnology for Identification of Endophytes Using Conventional and Molecular Tools

Frontmatter

8. Identification and Determination of Characteristics of Endophytes from Rice Plants

Abstract
Rice is the staple food of more than half of the world’s population. It is considered the oldest and the most important crop throughout the world, especially in Asia. Considerable agricultural areas are under cultivation of rice in the world. Studies on beneficial microbial interactions that lead to plant health and development are significantly increasing. Local and systemic colonizing microorganisms of plant tissues that have beneficial effects, such as increasing access to food or suppressing pathogens, are parts of endophytic populations. In this article, we tried to highlight the recent studies about identification and determination of characteristics of endophytes from various rice cultivars in the world. Numerous evidence show that rice plant harbors beneficial bacterial endophytic communities. These endophytes have many capabilities including plant growth-promoting activity, plant protection against biotic and abiotic stresses, and synergistic interactions with root-colonizing bacteria, which, in turn, are all in the direction of sustainable agriculture for sustainable agriculture development.
Hadis Yousefi, N. Hasanzadeh

9. Unraveling Plant-Endophyte Interactions: An Omics Insight

Abstract
Plants are home to a wide assemblage of nonpathogenic microbial community belonging to different phyla, bacteria, fungi, actinomycetes and viruses, the collective term for which is called endophyte. These endosymbiotic individuals exhibit endophytism principally by assisting in vigor and endurance to host plant and protect them from biotic (pathogenic infections) and abiotic stress (water, heat, nutrient, salinity, and herbivory). In return, these endosymbionts receive energy in the form of carbon from the host tissue. Colonization of endophyte in the internal tissues has been reported almost in every plant examined so far either in intercellular or intracellular mode. The form of relationships established with the host plant may be mutualistic, symbiotic, commensalistic, and trophobiotic. These are either rhizospheric or phyllospheric in origin. To establish such mutualistic relationships between plants and endophytes, certain chemical signals play important role in inducing production of the enhanced amount of secondary metabolites in host plant tissues. These novel metabolites act as a very good source of stress relievers to host and protect from grazing animals. The renewed interest in endophyte is due to the biotechnological relevance of these signal molecules as these have been used as a good source for production of biochemical compounds of industrial importance more specifically in agriculture and medicine. Additionally, their capacity to decontaminate soil bacteria and bring in soil fertility invites huge application in phytoremediation. However, the physiology, biochemistry, and genetics behind such complex interactions, exchange of chemical signals, and their production (the endophytism of plan-microbiome) are still half-understood. With the advent of new efficient analytical technology in molecular biology and genomics, the basic information on the existing diversity, phylogenetic lineage, evolution, and ecophysiological information about these endophytes has been tried to understand. However, the functional gene expression, posttranslational modifications, and protein turnover under various environmental circumstances are only revealed through transcriptome and proteomics analysis. Soon, high-throughput next-generation sequencing technology has remarkably changed the whole scenario of solving the intricate issues entangled with the complexity underlying endophytism. Sequencing of the whole genome of individuals following cultivable method (genomics), multiple host plants and their microbiome (comparative genomics), non-cultivable methods (metagenomics and metatranscriptomics), and microarray has been proved to be potential approaches to unravel the truth behind the plant-endophyte interactions. The present script deals with scopes, prospects, and outcomes of use of these “omics tools” to understand the deep insight into the mechanism of plant host infestation, biological reason behind the mutualism between host and endophytes, exchange of biochemical compounds, enhanced production of secondary metabolite, and host plant ecology.
Enketeswara Subudhi, Rajesh Kumar Sahoo, Suchanda Dey, Aradhana Das, Kalpana Sahoo

10. Isolation of Endophytes: The Gold Standard?

Abstract
Endophytes live in the internal tissues of plants without causing any visible damage to their hosts. They provide many beneficial effects to their hosts which range from promoting the plant growth to providing protection against various biotic and abiotic stresses to the host. They have also been considered to play direct or indirect roles in the synthesis of various biomolecules obtained from their host. However, most of the endophytes isolated and characterized so far have been culture dependent, and their number has been very low. Culture-independent studies of endophytes include high-throughput assays like transcriptomics, proteomics, etc. These high-throughput assays have predicted much higher numbers of endophytes as compared to the culture-dependent studies. The high-throughput assays have helped in deciphering the phylogenetic analysis of the whole microbiome of the plant and indicated very strong and deeper role of the endophytes in the host than anticipated before. However, in the absence of any gold standard approach for isolation and proper characterization of these endophytes, the high-throughput omics-based assays remain isolated to the particular hosts only. Their true potential in agriculture or crop protection will not be utilized. Therefore, the complex interaction of endophytes with their hosts needs to be studied by combining the omics-based assays with the culture-dependent methods, which can actually provide the true study material and their appropriate analysis.
Binay Chaubey

Production of Useful Metabolites

Frontmatter

11. Pharmaceutical Potential of Marine Fungal Endophytes

Abstract
The marine environment is currently well explored as one of the most essential sources regarding to natural products in research, since organisms from oceans have exhibited exceptional biological, biochemical, and biosynthetic potential. Similarly, microorganisms’ natural products represent a substantial area for novel therapeutic compounds search. Many reviews highlighted microbial metabolites as targets for discovery and development of new drugs, especially anticancer, antibiotics, antifungals, and antiparasitics among others. Marine fungal endophytes are therefore virtually unlimited sources of novel compounds with numerous potential therapeutic applications due to their immense diversity and proven ability to produce natural products of medicinal and pharmaceutical importance, thus inspiring researchers to further study them. This book chapter reviews some of the endophytic fungi isolated from marine sources that produce metabolites with various biological activities against human pathogenic microorganisms. The potential for the exploitation in the pharmaceutical industry and concerns are also discussed.
Rajesh Jeewon, Amiirah Bibi Luckhun, Vishwakalyan Bhoyroo, Nabeelah B. Sadeer, Mohamad Fawzi Mahomoodally, Sillma Rampadarath, Daneshwar Puchooa, V. Venkateswara Sarma, Siva Sundara Kumar Durairajan, Kevin D. Hyde

12. Diversity of Plant Endophytic Volatile Organic Compound (VOC) and Their Potential Applications

Abstract
Plant endophytes ranging from bacteria to fungi produce a diverse class of volatile organic compounds (VOCs) that are important for the development of symbiotic relation under highly competitive environment with the host. Not only that, they also play an important role in intra- and inter-kingdom signalling. Chemically, this gas-phase mixture may contain acids, alcohols, aldehydes, aromatics, esters, heterocycles, ketones, terpenes, thiols, and so forth. Several evidences suggested their potential use for sustainable crop production and industrial applications. Many VOCs have been reported with significant effects for antibiosis and growth promotion. They provide for an alternative to chemicals used to protect plants from pathogens and thus allow for better crop welfare. They also possess food and flavor properties which can be exploited in depth for food industries. Recent studies revealed that endophytes also produce diverse volatile hydrocarbons with fuel properties. They emit mixtures of volatile biofuel molecules comprising of alkanes, alkenes, acids, benzene derivatives, esters, etc. A vast diversity of endophytes are associated with plants for their ecology and fitness, and a systematic exploration of their VOCs will likely uncover novel use for their future utilization. In this chapter we highlight the nature and known or proposed functions of endophytic bacterial and fungal VOCs with a focus on the ones which have potential applications.
Farhana Tasnim Chowdhury, Mohammad Riazul Islam, Md. Rakibul Islam, Haseena Khan

13. Antidiabetic and Antioxidant Activities of Bioactive Compounds from Endophytes

Abstract
The aim of the present chapter is to appraise the phytochemical and pharmacological potential of the endophytes. This chapter will further highlight the future research prospects of the study of endophytes with antioxidant and antidiabetic activities. Informations on endophytes were obtained from related publications using electronic scientific databases. Based on previous reports, it could be said that the endophytes have emerged as excellent source of compounds which could be used for the treatment of skin diseases and microbial infections and as anticancer and anti-inflammatory agents. The studies provide new knowledge on the isolation and characterization of novel bioactives especially in the discovery of novel therapeutic drugs with antioxidant and antidiabetic properties. however, current research on the pharmacological properties of all the endophyte species including bioassay-guided isolation of phytoconstituents and their mechanism of action, pharmacokinetics, bioavailability, efficacy, and safety should be carried out in the future to add more value to this study.
Rosa Martha Perez Gutierrez, Adriana Neira González

14. Fungal Endophytes: A Novel Source of Cytotoxic Compounds

Abstract
Across the globe, cancer is the second most significant cause for mortality that was responsible for 8.8 million deaths in 2015, and the count is increasing at the alarming pace each year. The longer treatment protocols and the serious side effects of the existing anticancer drugs represent an urgent need to develop safe and effective anticancer drugs. Endophytic fungi offer the prolific source of novel metabolites that bears unique structural and functional capabilities with cytotoxic activity. In recent years, various bioactive metabolites possessing structural diversity have been identified from endophytic fungi and evaluated for their anticancer properties. Bioactive metabolites from endophytic fungi have potential to serve as a lead molecule for the pharmacological sector in the development of new drugs. The lower yield of metabolites is a major barrier for the utilization of these molecules for the treatment of cancer; therefore, alternate sources and production methods have been developed. The culture optimization to enhance yield and epigenetic means to activate silenced genes capable of producing novel metabolites were developed to obtain the fungal metabolites in higher quantities. The present review provides a comprehensive data of bioactive metabolites isolated from endophytic fungi harboring terrestrial plants during 2012–2018 (up to June 2018) with focus on their chemical structure, their cytotoxic capabilities, and their mechanism of action. The outlook of epigenetic modulation is discussed in perspectives of enhancing yield and identification of unidentified metabolites.
Sunil K. Deshmukh, Manish K. Gupta, Ved Prakash, M. Sudhakara Reddy

15. Endophytes as a Source of High-Value, Bioactive Metabolites

Abstract
Endophytes, microbes that reside within plants, are capable of producing high-value bioactive metabolites with diverse biological activities such as antimicrobial, insecticidal, antidiabetic, antioxidant, anticancer, etc. Endophytes thus represent a subset of microbes that reside in unique niches and, if explored properly, may prove to be a reservoir of bioactive principles. Despite this, less than 5% of total plant diversity has been screened for its endophyte content. Moreover, detailed examination of natural products and their bioactivities have been carried out for even lesser number of endophytes. Further, genome sequencing of several microbes has revealed that the potential of microbes to produce secondary metabolites has been substantially underestimated because many of the secondary metabolite biosynthetic gene clusters are silent under standard laboratory growth conditions. This chapter provides an overview of microbial natural products that have been isolated from endophytes and discusses the above issues and possible mitigation strategies.
Nitika Kapoor, Vijay Lakshmi Jamwal, Sumit G. Gandhi

16. Current Understanding and Future Perspectives of Endophytic Microbes vis-a-vis Production of Secondary Metabolites

Abstract
Endophytes are the bacterial and fungal forms of organisms living within the plant system causing no ill effects to the hosts. They asymptomatically live in the cellular environment in the plants carrying out various complicated functions such as production of secondary metabolites and signaling molecules coupled to the responses of various external and internal stimuli for mutual survival. They are known to produce a range of metabolites of utility in treating various disorders in humans and also produce chemicals of utility in agriculture such as growth regulator and pesticides, in several economically important plants. Continued research findings on the range of metabolites produce by them and their promising utilities have raised hopes in finding biotechnological solutions ranging from prospecting to production of industrial relevance to find lasting sustainable solutions for economical exploitation. These aspects have been dealt in detail as evidenced through current scientific understanding coupled to the future perspectives.
Shashank A. Tidke, S. Kiran, P. Giridhar, Ravishankar A. Gokare

17. Secondary Metabolite Production by Endophytic Fungi: The Gene Clusters, Nature, and Expression

Abstract
With the recent advancements in drug discovery, the bioprospecting of endophytic fungi for the search of secondary metabolites of pharmaceutical importance and novel medicinal properties has become one of the prime targets. The biosynthetic pathways that are responsible for secondary metabolites have genetic basis for their production. But the expression of the gene clusters responsible for secondary metabolites remains cryptic under laboratory conditions. The large-scale production of these metabolites is severely distressed by its attenuation in axenic cultures. Our insights into these clusters, their regulation, and expression may lead to the mining of more novel bioactive metabolites. This approach of genome mining for the production of novel metabolites is assuring. Major challenges lie in the understanding of the regulatory mechanisms which drive the expression of these cryptic genes. Gaining knowledge on various strategies for the identification as well as induction of these silent clusters is the need of the hour. With the help of multidisciplinary scientific approaches involving bioinformatics, molecular genetics, genome mining, metabolomics, etc., we can explore the hidden treasures of the endophytic fungal diversity.
Mishra Rashmi, V. Venkateswara Sarma

18. Secondary Metabolites Produced by Endophytic Fungi from Marine Environments

Abstract
Endophytes are symptomless organisms thriving within the living host tissues. Some endophytic fungi have been shown to be producing the same compounds produced by their hosts, e.g., taxol produced by Pestalotiopsis microspora isolated from Taxus wallichiana. Hence, there has been lot of interest to screen the secondary metabolites of endophytic fungi. In recent times the focus on endophytic fungi and the secondary metabolites they produce has shifted to marine environments. Unlike terrestrial environments where more research has been conducted on secondary metabolites from living plant substrata, the secondary metabolites produced by endophytic fungi isolated from marine environments are equally from macroalgae (seaweeds) and sponges in addition to mangrove and different shoreline plant substrata. Many promising secondary metabolites that have therapeutic potential including in antimicrobial, antiviral, antimalarial, and anticancer applications have been reported from endophytic fungi isolated from seaweeds, sponges, and plants from maritime environments. For example, the compound 3-O-methylfunicone isolated from Talaromyces sp., in mangrove habitat, has shown antifungal, antitumor, and lipid-lowering properties and required beyond academic research wherein pharmaceutical industry needs to take it further. A Cladosporium L037 species from the brown alga Actinotrichia fragilis, collected off Seragaki Beach at Okinawa Island, Japan, produced two 12-membered macrolides, namely, sporiolides A and B. Both these metabolites exhibited potent cytotoxicity against murine lymphoma L1210 cells with IC50 values of 0.37 and 3.1 um, respectively. A cyclic tetrapeptide compound produced by Petriella sp., an endophyte of the sponge Suberites domuncula, showed cytotoxicity against murine L5178Y lymphoma cells at an ED50 value of <0.1 μg/ml. The present chapter updates and consolidates the information available on the secondary metabolites produced by endophytic fungi isolated from marine environments.
Mishra Rashmi, J. S. Kushveer, V. Venkateswara Sarma

19. Fungal Endophytes from Medicinal Plants as a Potential Source of Bioactive Secondary Metabolites and Volatile Organic Compounds: An Overview

Abstract
In this chapter, we provide a general overview of secondary metabolites, especially easily volatilized molecules, namely, VOCs, isolated and identified from endophytic fungal communities of different medicinal plants. A fungal endophyte spends the whole or part of its life cycle colonizing inter- and/or intracellularly inside the healthy tissues of the host plants, causing no apparent symptoms of disease. Endophytic fungi produce a wide array of secondary metabolites and volatile organic compounds with important biological functions, displaying a broad range of useful antibiotic and pharmaceutical activities as well as immunomodulatory and toxic activities. Some of their biological activities are still unknown to mankind. These microbial metabolites have drawn enormous attention as potential agents of medicinal properties. Fungi are well known for emitting a complex mixture of volatile organic compounds (VOCs). Fungal VOCs commonly form a bioactive interface between plants and numerous microorganisms. Fungi emit plethora of unique volatile compounds that belong to a number of chemical classes including alcohols, aldehydes, acids, ethers, ketones, hydrocarbons, terpenes, and sulfur compounds. VOCs are gases, carbon-based compounds having characteristic odors, and are produced during primary and secondary metabolism. The diverse functions of fungal VOCs can be used in biotechnological applications as biofuel, biocontrol, and mycofumigation.
Humeera Nisa, Azra N. Kamili

Applications in Agriculture and Industry

Frontmatter

20. Endophytic Fungi: A Cryptic Fountainhead for Biodiversity, Functional Metabolites, Host Stress Tolerance, and Myco-mediated Nanoparticles (Nps) Synthesis

Abstract
The view on association of higher plants and fungi from past few decades confirms the belief that all plants foster their own endophytic fungal diversity as a host, and all plant species studied till date are found to harbor one or more endophytes. The diversity of endophytic fungi can have deep impressions on plant communities through adding fitness to their concerned host conferring tolerance against abiotic and biotic stresses. While endophytes have been outlined to biosynthesize a wide array of molecules, genome sequencing of such organisms has revealed that these have the potential to provide many more secondary metabolites than usual. Recently, various methods have been advanced to aid in the activation of cryptic biosynthetic pathways. Since the most important medicinal compound taxol (paclitaxel) has been isolated from the endophytic fungus therefore, more plant mimetic compounds may be expected from this hidden microbial source. Various enzymes (amylase, lipase, cellulase, protease, lactase, pectinases, peroxidase, catalase, and penicillinase) and toxins (aflatoxin, zearalenone, ochratoxin, citrinin, T-2 toxin, and fumonisins) may be isolated from this repertoire. Cell-free extract of many endophytic fungal isolates may also be utilized to synthesize the nanoparticles like copper (Cu), silver (Ag), platinum (Pt), and gold (Au) from respective metal salt solutions. This chapter also discusses different approaches such as co-culture of microbes, altering growth media and culture conditions, genetic as well as epigenetic strategies for obtaining the biochemical treasure hidden within these unique microbes.
Jay Hind Nishad, Arti Singh, Veer Singh Gautam, Dharmendra Kumar, Jitendra Kumar, R. N. Kharwar

21. Endophytes as a Source of High-Value Phytochemicals: Present Scenario and Future Outlook

Abstract
Endophytes, a group of microorganisms that reside within plants, are promising eco-friendly source of high-valued bioactive phytochemicals that are produced by their host. Some of the well-known examples of phytochemicals produced by endophytes are Taxol, camptothecin, azadirachtin, podophyllotoxin, vinca alkaloids, cinchona alkaloids rohitukine, and many others. The molecular machinery for production of phytochemicals in endophytes is likely acquired from the host plant. After growing in axenic conditions for a few generations, the endophyte generally undergoes attenuation, and the production of phytochemical may reduce to a great extent or stop completely. Genome sequencing of several endophytes revealed that complete biosynthetic pathways for production of phytochemicals may not be present or if present the genes may not be homologous to the plant genes. Other possible reasons for attenuation as well as experimental methods through which the issue of attenuation may be addressed have also been discussed in the chapter.
Vijay Lakshmi Jamwal, Sumit G. Gandhi

22. The Interaction Between Plants and Bacterial Endophytes Under Salinity Stress

Abstract
Salinity leads to a decline in agricultural production and an increase in the percentage of salinity-affected land which exceeds 20% of the world’s cultivated land. Endophytes are a class of endosymbiotic microorganisms widely distributed among plants and colonize intercellular and intracellular spaces of all plant compartments and do not cause any apparent infection or significant morphological change. Furthermore, endophytes have many beneficial effects on host plants including adaptation to biotic and abiotic stress such as salinity through different activities including the production of scavengers like reactive oxygen species that are produced in plants when exposed to salinity, production of ACC deaminase enzyme which is responsible for lowering the levels of ethylene in the plant, nitrogen fixation, production of compatible solutes, antibiotics, and phytohormones. The use of endophytic microbes is of particular interest in the development of agricultural applications that ensure improved performance of crops under salinity stress.
Amr Fouda, Saad El Din Hassan, Ahmed Mohamed Eid, Emad El-Din Ewais

23. Endophytes as Pollutant-Degrading Agents: Current Trends and Perspectives

Abstract
Bioremediation is based on biological systems, bacteria, fungi, and plants. They are effective systems to treat a polluted site because they are able to modify the chemical structure of the contaminant into less hazardous end products. Investigations regarding the theme have immensely accelerated during the last years, what originated a great number of articles involving the terms “phytoremediation” and “bioremediation.” Initially the term phytoremediation was defined as being the use of plants for the degradation of polluting hazardous chemicals. However, the discovery that healthy plants could be containing endosymbiotic groups of microorganisms, often bacteria or fungi, led to the notion that these microorganisms could be, partly at least, responsible for the degradation of the pollutants. This review focuses on this proposed partnership in the bioremediation process, taking into account investigations conducted during the last 5 years.
Rúbia Carvalho Gomes Corrêa, Daiane Iark, Andressa de Sousa Idelfonso, Thais Marques Uber, Adelar Bracht, Rosane Marina Peralta

24. Fungal Endophytes: Rising Tools in Sustainable Agriculture Production

Abstract
Endophytes are the microorganisms that lived inside the plant during their life cycle and develop a mutualistic or symbiotic relationship with the host plant. In mutualistic relation, the plant provides nutrition to endophyte, and in return endophyte supports the plant growth and induces immunity in the host by producing secondary metabolites. These secondary metabolites play a significant role in the inhibition of plant pathogen and pest by inducing plant defense. Some of them take part in the induction of salicylic acid, jasmonic acid, and ethylene pathways which are responsible for plant defense. Different microbes like nitrogen-fixing bacteria and mycorrhizal fungi have been explored for decades in sustainable agricultural practices; some of them are being used at a commercial level. But the role of endophytes in plant stress tolerance (biotic and abiotic) and their commercial utilization is not much explored, and researchers are only screening endophytic microbial potentials in bio-fertilizer and bio-pesticide application at lab scale. The role of bioactive compounds from fungal endophytes in sustainable agriculture is least explored. Exploration of natural phenomena of such fungal endophytes and their compounds in crop production and protection is the need of present scenario which is facing problems of pollution with synthetic chemicals and their detrimental impacts on the environment. In the current chapter, we reviewed the role of fungal endophytes and their bioactive compounds in crop production and protection. Detailed analysis of endophytes and their bioactive compounds in plant protection (antibacterial, antifungal, insecticidal, and nematicidal) and growth promotion under different abiotic stress has been presented. The challenges and limitations in commercial agricultural product development of fungal endophytes are also discussed in the chapter.
Hemraj Chhipa, Sunil K. Deshmukh

25. A Thorough Comprehension of Host Endophytic Interaction Entailing the Biospherical Benefits: A Metabolomic Perspective

Abstract
Endophytism is the phenomenon of in planta residency and mutualistic association of microbes with hosts without causing any disease symptoms. The multifaceted attributes of endophytes include plant growth promotion as well as resistance of the host to several forms of abiotic or biotic stresses. Moreover, endophytes are reported to manipulate the rhizospheric microbiota as well as the microbiota present within plants so as to amplify the host beneficial mechanisms. Endophyte mediated host beneficial traits become far more significant owing to the differential recruitment of endophytes by host under varying root exudate profile, host’s age, as well as host-endophyte compatibility. However, in spite of such beneficial attributes, our understanding of endophytes is still quite limited and inadequate. Thus, the true potential of endophytes can be particularly harnessed when we gain a thorough insight on the molecular mechanisms responsible for mutualistic host-endophyte interaction. In this chapter, we present an exhaustive investigation of endophyte-plant interaction, beginning from chemotactic attraction of the supposed endophytic microflora from soil to establishment of endophytism. We will also focus on the endophyte-directed metabolite biosynthesis aiding in effective host functioning.
Shatrupa Ray, Jyoti Singh, Rahul Singh Rajput, Smriti Yadav, Surendra Singh, Harikesh Bahadur Singh

26. Endophyte-Mediated Host Stress Tolerance as a Means for Crop Improvement

Abstract
Plants being sessile are continuously exposed to a wide range of biotic and abiotic stresses that exert adverse effect in their growth and development. Various physiological, biochemical, and molecular machineries are employed by the plants to overcome these stresses. Endophytes are mostly the symbiotic fungi and bacteria that reside inside the plant tissue and stimulate plant growth during stress conditions. Endophyte-mediated plant stress tolerance holds significant role in the analysis of plant-microbe interactions. Although still at its infancy, the endophyte-mediated host stress tolerance including drought, salinity, high-temperature stresses, and pathogenic infection has been well described in the recent times. The molecular mechanism governing the endophyte-mediated stress response includes the induction of plant stress genes and regulation of reactive oxygen species. In the present review, we discuss the evidences for bacterial and fungal endophyte-mediated stress tolerance and associated mechanisms. This information from this review will help the scientific community in the development of suitable biotechnological approaches toward usage of endophyte microbes in the improvement of crop yield under multiple stress conditions.
Satyabrata Nanda, Bijayalaxmi Mohanty, Raj Kumar Joshi

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