Numerous microorganisms exist in mutualistic associations with plants, whereby their interaction results in a beneficial outcome for both entities. Microbes with such capabilities are ample in above-ground as well as in underground (edaphic) habitats. Epiphytes are microorganisms that are found on the external surface of plants, whereas endophytes are microorganisms that reside and establish themselves within plant tissues, specifically within the leaves or roots. Among these, the rhizosphere harbors a plethora of active microorganisms that enhance plant nutrition, growth, and development of plants. The rhizosphere can be defined as the soil zone in the proximity of plant roots that is affected by the presence of microorganisms and root exudates, including compounds secreted by the root system of the plants (Kanchan et al., 2020). The region is characterized by multifaceted plant-microbe interactions, encompassing mutualistic, symbiotic, or parasitic relationships. These interactions are capable of triggering the biosynthesis of secondary metabolites by the microbial cells, which can be advantageous for the plants by conferring tolerance to biotic and abiotic stresses contributing to the plant’s overall fitness (Koza et al., 2022). Endosymbiotic microorganisms, which are typically bacteria and/or fungi, establish mutually beneficial relationships with their plant host including improved host fitness. These organisms are considered to be non-pathogenic since they can complete a part of their life cycle or even the whole life cycle within their host without causing any symptoms of disease (Nair and Padmavathy, 2014). The endophytic community can be further divided into two subgroups which involve ‘obligate endophytes’ (endophytes that critically dependent on plant metabolism for their survival) and ‘facultative endophytes’ (endophytes that spend certain stages of their life cycle outside the host body and are mostly associated with plants present in their nearby soil environment) (Hardoim et al., 2008; Abreu-Tarazi et al., 2010).

Of all the microorganisms inhabiting the rhizosphere, endophytic fungi or fungal endophytes have garnered significant attention from researchers. This is owing to their ability to produce various bioactive molecules such as antibacterial compounds, and biostimulants, which can facilitate essential oil biosynthesis (Radic and Strukelj, 2012; Uzma et al., 2018; El Enshasy et al., 2019). Essential oils are the aromatic compounds that have high vapor pressure and low boiling point. Vanillin and 3-methoxy-4-hydroxytoluene was isolated from the roots of Zingiber officinale Rosc. infected with Streptomyces aureofaciens SMUAc130 (Taechowisan et al., 2005). The bacterial volatile compounds are significant in establishing interspecific and or intraspecific communication and role in defence mechanism against antagonistic microbes. Volatile organic compounds (VOCs) play extremely important role in antibiosis and signaling mechanism for microbes with symbiotic relation under competitive soil conditions (Polito et al., 2022). Endophytic fungi have been recognized for their multifaceted roles in plant-microbe interactions: nutrient solubilization in the plant rhizosphere, promoting plant growth, acting as biocontrol agents against pests and pathogens, inducing systemic resistance against biotic and abiotic stresses, and participating in the biosynthesis of secondary metabolites (Mehta et al., 2019; Poveda et al., 2020a; Cui et al., 2021; Poveda et al., 2021; Poveda and Baptista, 2021). Fungal secondary metabolites may act by causing alterations in the host plant’s morphology and physiology (Alam et al., 2021). Endophytic fungi establish symbiotic associations with host plants through a process that involves the enzymatic degradation of the host plant’s cell wall. To colonize the host plant tissue, endophytic fungi produce a range of cell wall-degrading enzymes including cellulase, laccase, pectinase, and xylanase. These enzymes facilitate the infiltration, colonization, and proliferation of endophytic fungi within the host plant tissue by altering the physical and structural properties of the host cell wall (Chow and Ting, 2019). Upon degradation of the host plant cell wall, host plant activates its defence mechanisms such as pattern-recognition receptors (PRRs) which provide innate immunity to the plant. In order to survive in plants, the endophytes require specific strategies to avoid being detected by the plant based immune system. One such strategies include, hiding of chitin by modifying it or oligomers derived from chitin employing chitin deacetylases (Cord-Landwehr et al., 2016). Apart from these, many fungal endophytes have been identified to secrete bioactive compounds known as secondary metabolites, which are helpful in coping with biotic and abiotic stresses. These secondary metabolites include mostly alkaloids, terpenoids, polyketides. Besides these major ones, certain secondary metabolites are also secreted such as flavonoids, saponins, phenols, and phenolic acids, aliphatic and chlorinated metabolites, peptides, and steroids. It was found that similar secondary metabolites are being produced by the fungal endophytes and even in larger concentrations as compared to the plants. Using gene clustering, transcription factors and horizontal gene transfer, we can study the biosynthesis pathways and genes encoding specific types of bioactive molecules.

Fungal endophytes are emerging source for terpenoids, an important class of secondary metabolites. Terpenoids are a diverse group of natural products, which consist of C5 isoprene units and are the largest class of natural products (Perveen, 2018). The structural diversity of terpenoids is substantial, with more than 80,000 terpenoids having been identified from both plant and microbial sources. The isoprene units required for terpenoid biosynthesis are typically synthesized through either the mevalonic acid pathway (MVA) or the methylerythritol phosphate pathway (MEP). Terpenoids exhibit a diverse range of pharmacological and nutritional activities, as well as utility in the food and cosmetic industries. Moreover, their therapeutic potential has been explored in the context of COVID-19 treatment due to their notable antiviral properties (Diniz et al., 2021). Due to these activities, there is increase in demand of terpenoids which imposes a strain on the terpenoid-producing plant species. A wide variety of terpenoids are produced by endophytic fungi but none of them is capable of producing terpenoids at commercial scale as their yield is low, especially after repeated subculturing.

Initially, with the advent of first generation sequencers alongwith amplicon based sequencing for variable regions of genomes was being employed for deciphering microbiome understanding. However, extensive studies on root morphology and root exudation in deciphering rhizobiomes can be done employing next generation sequencing (NGS). Metagenomics allows detailing of complete genomic information by assembling DNA sequences into genes. It also provides information about novel genes, bio based-products, biomolecules, interaction between microbial communities. Whereas, transcriptomics utilizes the NGS based information to identify and quantify the presence of the particular RNA molecule in biological samples. Metabolomics, on the other hand is a technique which is utilized to identify and analyze metabolite changes occurring due to overexpression or mutation in a desired gene (Chen et al., 2022). The combination of various omics-based approach can help in better understanding of plant-endophyte interaction mechanisms. This study focusses on the secondary metabolites (especially those of terpenoid nature) secreted by endophytic fungi. The study elaborates the role of endophytic fungi as potential source of terpenoid producer alongwith its host related molecular interactions. Concomitantly, a noteworthy discussion on recent multi-omics based approaches employed to have better understanding of host and endophytic fungi interaction for secondary metabolite production.

Endophytic fungi (EF), also known as fungal endophytes, are communities of fungi that form associations either inter- or intracellularly with host plant tissues while simultaneously providing benefits to the host and gaining benefits from it (Alam et al., 2021). These fungi establish a mutualistic or symbiotic relationship with the host plant, and are categorized into two groups based on this relationship. The first group is the Clavicipitaceous fungi or Balansiaceous group, which includes class I endophytes. This group comprises free-living symbiotic species that survive in cool season grasses (Poaceae), infect the ovules of host plants, and are transmitted vertically to progenies through host seeds. The living rhizomes and shoots of the host plant are colonized by these endophytes. The second group is the Non-Clavicipitaceous fungi or Non-Balansiaceous group, which includes class II, class III, and class IV endophytes. The Class I endophyte species are considered as obligate endophytes that offer protection to their host plant under conditions of drought stress, by secreting bioactive metabolites that exhibit defensive or supportive properties (Roberts and Lindow, 2014; Poveda et al., 2021). Non-Clavicipitaceous fungi or Non-Balansiaceous group (includes class II, class III and class IV endophytes) are non-grass host related groups having extensive biodiversity and distribution. These endophytes reside within plant tissues in a dormant or quiescent state without causing any apparent harm to the host plant, that is, they are not closely associated with the host plant. However, as soon as the chemical changes in the host plant occurs either through injuries or environmental stresses, these EFs then enter the host plant intracellularly through roots shoots or rhizomes (Carroll, 1988; Rodriguez et al., 2008; Mishra Y. et al., 2021). In Class II endophytes colonization of the host tissue occurs through roots, shoots and rhizomes whereas colonization occurs through shoots only and roots only in class III and class IV endophytes, respectively. The transmission occurs both vertically and horizontally in class II endophytes whereas only horizontally in class III and class IV endophytes (Rodriguez et al., 2009). Brief list of important crops and beneficial endophytic fungi with their respective functions have been provided in Table 1.

Endophytic fungi are capable of producing a diverse range of bioactive compounds that exhibit a wide array of biological activities including, but not limited to, insecticidal, antioxidant, antifungal, antiviral, antibacterial, and cytotoxic properties. These compounds belong to various chemical classes such as terpenoids, phenols, alkaloids, polyketides, quinones, steroids, enzymes, and peptides. The secretion of these bioactive compounds by endophytic fungi is known to host plant defence response, enabling it to better cope with both biotic and abiotic stressors. Methods to enhance the potential of endophytic fungi for producing these secondary metabolites include the activation of silent biosynthetic pathways, epigenetic modifications, and other techniques. Among these secondary metabolites, terpenoids have emerged as a particularly important class of molecules that have significant applications in human health and agriculture. Thus, endophytic fungi represent a promising novel source for the bioproduction of these valuable terpenoid compounds. The isoprene units are typically obtained through two pathways, the mevalonic acid pathway (MVA) and the methylerythritol phosphate pathway (MEP). Based on the number of carbon atoms in their skeletal structure [(C₅)_n], terpenoids can be classified into various subgroups, including hemi terpenoids (C₅), monoterpenoids (C₁₀), sesquiterpenoids (C₁₅), diterpenoids (C₂₀), sesterterpenoids (C₂₅), triterpenoids (C₃₀), and tetraterpenoids (C₄₀) (Gershenzon and Dudareva, 2007).

The building blocks of terpenoids, which are a diverse group of natural products, are isopentenyl pyrophosphate and dimethylallyl pyrophosphate. These are synthesized through the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways, and are interconvertible by the action of isopentenyl pyrophosphate isomerase. Subsequently, prenyltransferases convert these shorter chain precursors to longer chain terpenoid skeletons, such as geranyl diphosphate, farnesyl diphosphate and geranylgeranyl diphosphate, which serve as the C10, C15, and C20 backbones of monoterpenoids, sesquiterpenoids and triterpenoids, diterpenoids and tetraterpenoids, respectively. Further structural diversification of terpenoids can be achieved by the introduction of functional groups, such as glycosyl, hydroxyl, ketone, carbonyl, and aldehyde, or by rearrangement of the carbon skeleton. These modifications can lead to the expression of various bioactivities associated with terpenoids (Sun et al., 2019). Numerous plant species are recognized for their capacity to biosynthesize terpenoids, including citral, menthol, camphor, salvinorin A (in the case of the plant Salvia divinorum), ginkgolide, and bilobalide (in the case of the plant Ginkgo biloba), and cannabinoids (in the case of the cannabis plant). Terpenoids are also commonly synthesized by tea, thyme, Spanish sage, and citrus fruits (such as lemon, orange, and mandarin). These terpenoids exhibit diverse functions in the food and cosmetic industries, as well as various pharmaceutical and nutritional applications. Furthermore, terpenoids have demonstrated good antiviral activity, and have therefore been investigated for their potential clinical use in the treatment of COVID-19. Due to these activities, there is an increase in demand of terpenoids which possess stress on the terpenoids producing plant species. In order to fulfil the increasing demand of terpenoids, other sources which are environmentally friendly and commercially fulfilling need to be discovered. The endophytes have the potential of synthesizing these terpenoids which have gained the attention for using the endophytes for alternate source of terpenoid-producing strains or terpenoid synthetic genes (Chen et al., 2021).

Endophytic fungi and its host plant undergo various complex interactions which enhance the plants growth and nutrition, also helps the plant in combating various biotic and abiotic stress conditions. Endophytes are known to exhibit a high degree of variability that is dependent on several factors such as the genotype of the host plant, growth stage, physiological state, tissue type, soil environment, and various agricultural practices (Gupta et al., 2020). These microorganisms have been shown to not only produce terpenoids themselves, but also stimulate their production in host plants through mechanisms such as horizontal gene transfer, the heterologous expression of terpenoid biosynthetic genes sourced from endophytes, biotransformation of terpenoids, and various signaling pathways that include elicitor recognition, signal transduction, integration with transcription factors, and gene activation (Zhai et al., 2017). Numerous scientific methodologies have been created to advance terpenoid biosynthesis research. These include metabolic engineering and synthetic biology, system biology approaches, modern metagenomic sequencing methods, and the de novo assembly of microbial genomes from metagenome data. These techniques enable the expression of the terpenoid biosynthetic pathway in industrial microbes, increase the potential gene pool involved in terpenoid biosynthesis from various environments, and offer effective strategies for discovering novel microbes and genes related to terpenoid biosynthesis in the endosphere and rhizosphere microbiomes, regardless of their culturability (Carrión et al., 2019; Belcher et al., 2020). Huperzine A (HupA) is a naturally occurring sesquiterpene alkaloid that is synthesized by members of the Huperziaceae family, which includes species such as Huperzia serrata. HupA has been found to possess potent anti-acetylcholinesterase activity, making it an effective treatment option for Alzheimer’s disease (AD). Furthermore, HupA’s ability to effectively inhibit acetylcholinesterase has been associated with minimal side effects, highlighting its potential as a safe and effective treatment option for AD (Zhao et al., 2013). The enzymes lysine decarboxylase and copper amine oxidase catalyze the first two steps of HupA biosynthetic pathway in which L-lysine is converted to 5-aminopentanal which is the precursor of HupA. Researchers successfully isolated two strains of endophytic fungi, EFs Shiraia sp. Slf14 (Zhu et al., 2010) and Cladosporium cladosporioides LF70 (Zhang et al., 2019), from the leaves of Huperzia serrata. These strains were found to produce Huperzine A (HupA) and were able to yield 142.6 μg/g and 39.61 μg/g dry mycelium, respectively. On sequencing the whole genome of Shiraia sp. Slf14, HupA biosynthetic gene cluster was identified, which is then expressed into Escherichia coli, which showed that genetically modified E. coli strain was able to convert cadaverine to 5-aminopentanal (Yang et al., 2016). Afterwards, some other strains of EFs were isolated, such as Colletotrichum gloeosporioides ES026, which were then sequenced and expressed for its yield of 5-aminopentanal which is a precursor of HupA.

Traditionally utilized medicinal plants Nothapodytes nimmoniana and Campotheca acuminata contain campothecin which belongs to the class of monoterpene indole alkaloids and functions as potent topoisomerase inhibitor in DNA replication. Reports from various studies suggest that Entrophospora infrequens and Neurospora crassa isolated from N. nommoniana produce campothecin (Puri et al., 2005; Rehman et al., 2008). Kusari et al. (2009) suggested that Fusarium solani isolated from the barks of C. acuminata are potential source of campothecin production. The endophytic strain of F. solani utilizes enzymes encoded by its gene in presence of strictosidine synthase, one of the majorly important plant enzyme for the campothecin biosynthesis. Another report by Yan et al. (2019) suggested that ginsenosides Rh2 and Rg3 are produced by strain PDA-2 which is closely related to Agrobacterium rhizogenes which was isolated from Panax ginseng. The ginsenosides Rh2 and Rg3 have major roles in inhibiting tumor cell proliferation and induce apoptosis. In a study by Palem et al. (2015), authors have suggested biosynthesis of vincristine and vinblastine by endophytic fungus Talaromyces radicus isolated from various tissues of Catharanthus roseus. The study screened 22 endophytic fungi for presence of gene encoding tryptophan decarboxylase which could only be amplified in T. radicus. The gene tryptophan decarboxylase is one of the most important enzyme terpenoid indole alkaloid biosynthetic pathway. Maximum yield of 670 μg/L and 70 μg/L of vincristine and vinblastine from modified M2 medium and PDB medium was obtained, respectively. Parthasarathy et al. (2020) recorded the vinblastine production Curvularia verruculosa isolated from leaves of C. roseus. Maximum yield of 182 μg/L of vinblastine was obtained from endophytic fungi C. verruculosa.

Stress can be defined as any substance, microorganism or unfavorable condition which directly or indirectly affects the plant’s growth and development, metabolism or nutrition. Stress on vegetation depends on factors such as, temperature, mineral deficiency, long rainy periods, desiccation problems, insects and pathogens, herbicides and pesticides, pollutants, climatic conditions like drought or floods, increased UV radiations and so on. Based on the LICHTENTHALER model of stress in plants (Lichtenthaler, 1998), stress can be divided into several distinct phases. The first phase is the response phase, which is characterized by an alarm reaction and marks the beginning of stress. This is followed by the restitution phase, where the plant enters a stage of resistance and continues to experience stress. The third phase is the terminal phase, where the plant enters a stage of exhaustion after long-term stress. Finally, the regeneration phase allows the plant to recover and rejuvenate after experiencing stress. These phases of stress describe in detail the changes that occur in the plant during the unfavorable or stress conditions. Initially, there is decline in physiological functions which leads to decrease in metabolic activities and decline in growth, development and vitality of the plant. In response, the plant’s defence system gets activated leading to hardening of the plant by increasing the plant’s resistance against stressors by reaching plant resistance maximum. If the stressors are removed before senescence the plant survives via regeneration but if the stressors are not being removed then the plant leads to cell death which ultimately causes plant death (Lichtenthaler, 1998). Plant stressors can be divided into three types, that is, natural or abiotic stressors such as high light, heat, drought, mineral deficiency, low temperature, chilling, wounding, UV-A and UV-B, biotic stressors such as insects, pathogens, elicitors, bacteria, fungi and virus, anthropogenic stressors such as, herbicides, air pollutants, peroxyacyl nitrates, free radicals, acid rain, acid fog and heavy metal load. Plants sense these stressors and act accordingly via activation of signal transduction pathways after signal perception further leading to gene expression or metabolic responses in the plant. Under stress conditions, plants synthesize bioactive molecules such as phytohormones and secondary metabolites which not only have the tendency to overcome the stress conditions but also have antifungal, anticarcinogenic and various other medicinal properties which can be utilized to treat various diseases. EFs have the capability of producing the secondary metabolites (terpenoids, alkaloids, phenols, quinones) that would help in fighting the biotic and abiotic stress in plants as well as can be utilized in pharmaceutical industry due to its medicinal properties (Gershenzon and Dudareva, 2007; Christiansen et al., 2021).

When endophytic fungi interact with their host plant, the plant’s defence system is activated to counteract the presence of the endophytic fungi which are perceived as potential pathogens. However, endophytic fungi are capable of evading these defence mechanisms and colonizing the host plant. Subsequently, endophytic fungi produce bioactive compounds, such as terpenoids, phenols, alkaloids, steroids, quinones, poly-ketones, and peptides, which exhibit inhibitory effects on the growth of pathogens and herbivores invading the host plant in the presence of endophytic fungi (Lu et al., 2021). This phenomenon provides a protective mechanism to the host plant from pathogenic microorganisms. Various terpenoids are synthesized by endophytes which will help host plants to combat biotic and abiotic stresses. Examples of these terpenoids include indole diterpenoids, synthesized in endophytic infected grasses, are neurotoxins, responsible for intoxication, helpful in protecting the grass from cattle grazing (Hardoim et al., 2015) multi-cyclic indolosesquiterpene synthesized by Streptomyces sp. HKI0595 in Kandelia candel has antibacterial activity (Maier et al., 2011), cadinane sesquiterpene derivatives synthesized by Phomopsis cassia in Cassia spectabilis has antifungal activity against phytopatogenic fungi Cladosporium cladosporioids and C. sphaerospermum. Persicaria minor also known as kesum is herbaceous plant widely found in south-east Asia and is mainly important for flavonoid and terpenoid synthesis. Study by Samad et al. (2019) reported that six miRNAs of Persicaria minor post-transcriptionally regulated the terpenoid biosynthesis induced by Fusarium oxysporum.

A large diversity of microorganisms is present in the soil that interacts with the plants growing in that soil. These interactions are known as plant-microbe interaction. These interactions play a very important role in making a sustainable balanced ecosystem. Plants synthesize various organic and inorganic nutrients which makes the soil nutrient enriched that is very beneficial for the microbial consortia growing in that soil. Plants house endophytes which are one of the examples of plant-microbe interaction. Such interactions between plants and various microbes such as bacteria and fungi are beneficial and attract the interest of various researchers due to their potential for combatting biotic and abiotic stresses along with its application in agriculture. Throughout their life cycle, plants engage in the synthesis of two distinct categories of metabolites: primary and secondary metabolites. Primary metabolites, which are essential for the plant’s growth, development, and nourishment, remain constant across all plant species. In contrast, secondary metabolites function as signaling molecules that play a crucial role in signal transduction. These metabolites are typically secreted by plants in response to herbivore, pathogen, or environmental stress but in low quantities. However, research suggests that endophytes, particularly EFs, have the capability to produce these secondary metabolites in large quantities when compared to plants. There are several researchers working for the discovery of these secondary metabolites as these are potential source for depleting the use of chemical pesticides, insecticides or herbicides and these discoveries are categorized as: (a) metabolites that are unknown, (b) metabolites with known function but unknown structure, (c) metabolites with unknown function but known structures (Luo et al., 2022).

Researchers face several difficulties in the discovery of these secondary metabolites which include (1) metabolites are secreted by the plants in very low concentrations, (2) the metabolites that are being secreted and synthesized are being actively metabolized as well, (3) they have diverse physical and chemical properties which require specific assays to determine their functions and structures, (4) these metabolites are secreted at specific stages of the plant’s life which makes it difficult for scientists to discover them (Luo et al., 2022). To surmount the hurdles in the study of plant secondary metabolites, it is imperative to adopt interdisciplinary methods. A multi-omics approach, for instance, has been instrumental in the identification of these metabolites via the methodical comparative analysis of extensive datasets by researchers. In a broader aspect, “omics” are the scientific fields that are related to measuring biological molecules in high throughput methods. This includes various biological fields such as genomics, proteomics, metagenomics, metabolomics, phenomics, epigenomics, transcriptomics and so on. When all these fields are studied in an integrated manner for discovery of some biological molecule, then it is called a multi-omics approach. This review utilizes a multi-omics approach to investigate a diverse range of secondary metabolites synthesized by endophytes. By employing one or multiple omics approaches, a scientific experiment can be designed to align with the function and structure of the metabolite. Each omics approach has its unique characteristics and can complement the limitations of the other omics approach, thereby providing a comprehensive understanding of the endophytic secondary metabolite’s synthesis and its potential applications.

Genomics is the field of biology that deals with the study of the whole genome (including structure, function, evolution, mapping and editing of genome) of the organism. Genome is the whole sequence of the DNA set of the organism. The fundamental genetic material, DNA, contains essential information about the regulation of gene expression, including promoter regions, untranslated regulatory regions, and splicing sites, as well as the protein-coding sequence that determines the function of a given gene within an organism (Chu et al., 2020). The field of genomics is driven by advanced technologies such as high-throughput DNA sequencing techniques, such as Illumina HiSeq, PacBio, and Nanopore sequencing, as well as single nucleotide polymorphism (SNP) chips that enable the identification and analysis of genetic variations among individuals. The whole genome sequencing analysis would help us understand that which genes are responsible for growth and development, defence system, nutrient acquisition, production of secondary metabolites, and various other processes of the organism which we are studying. This approach of whole genome sequencing would help in determining the genes that are directly or indirectly influencing the various bioactivities or metabolic activities of the endophyte or plant which is synthesizing the secondary metabolites.

In the context of the interactions between endophytes and plants, various biotic and abiotic stresses may occur during their interactions leading to the production of secondary metabolites as a defence mechanism. Genomics approaches utilizing high-throughput sequencing techniques offer a powerful tool for identifying the specific genes responsible for the activation of signaling pathways leading to the production of secondary metabolites (Alam et al., 2021). Additionally, such approaches can be used to investigate plant growth promotion, endophytic secretory systems, surface attachment and insertion elements, transport systems, and other related metabolic mechanisms. This detailed knowledge about the genes and its functions would provide us with better understanding about the ecology and evolution of the endophyte and we could accordingly extract the gene responsible for secondary metabolite production and amplify it using PCR for its further utilization. Compounds like alkaloids, flavonoids, minerals, polyphenols and vitamins are mostly synthesized by endophytes have positive influence on adjusting in adverse conditions and hence, promoting plant health (Balestrini et al., 2021). These molecules/compounds can be detected and analyzed employing techniques such as gas chromatography–mass spectroscopy (GC–MS), Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, metabolite fingerprinting, time-of-flight mass spectrometry (TOF-MS), Orbitrap Mass Spectrometer (Orbitrap-MS), flash chromatography. The signaling pathway initiation and colonization factors due to host cell and endophytic interactions can be evaluated on the basis of proteomics studies. However, there are new omics tools available for deciphering the fungal genome and the metabolites produced by them through epigenomics, ionomics, fluxomics, lipidomics, nutrigenomics, toxicogenomics. By integrating these various techniques, the secondary metabolite production can be verified and analyzed at every level (Table 3; Shankar and Sharma, 2022). The host endophyte interaction from recognition phase to stress resistance development can be thoroughly studied via transcriptomic analysis.

During the investigation of the metabolic output of the colocalization phenomenon of prenyltransferase (Polyprenyl synt (PT)) and terpene synthase (Terpene synth C (TPS)) domains in plant genomes, the biosynthesis of sesterterpenes, a rare type of terpenoid, was discovered to occur in both plants and fungi (Huang et al., 2017, 2018). P. indica, has the potential of acting as plant probiotic agent, that has been revealed during its genome sequence analysis (Qiang et al., 2012). EFs of order sebacinales helps the host plant in enhancing its growth, development and stress tolerance potential, is revealed by this approach (Weiss et al., 2011). Several bioinformatic tools, such as plantiSMASH (Kautsar et al., 2017), phyto cluster (Töpfer et al., 2017), and clusterfinder (Schläpfer et al., 2017; Chavali and Rhee, 2018), have been developed to predict plant biosynthetic gene clusters (BGCs) using plant genomic sequences, protein annotations, and gene expression profiles. This facilitates the identification of plant secondary metabolites, which can have important implications in fields such as drug discovery and agriculture.

The development of a sustainable agriculture is of utter importance. Microorganisms like the endophytic fungi represent an intriguing area of study in the field of plant-microbe interactions in this context. The unique ability of these fungi to inhabit and colonize host plant tissues and thereby stimulate the production of wide range of secondary metabolites with diverse biological activities, including antifungal, antibacterial, anticancer, and immunomodulatory properties are of extreme importance. These attributes enhance the plants disease resistance ability, growth and nutrient uptake abilities. Most of these secondary metabolites produced by these fungi are valuable sources of antimicrobial, antitumor, and antiviral agents, among other bioactive compounds, making them a vital component in the development of new drugs. Multi-omics technologies can further help in deciphering the physiological development of endophytes in host plant. Concomitantly, generation of more high-throughput data will provide updated information on the core areas of study, thus discovering unknown genes, metabolites, and microbial species for better harnessing of beneficial aspects from endophytes. Thus, in conclusion it can be well understood that the overall, investigation of endophytic fungi and their metabolic products has gained significant attention in recent years, and this approach holds great promise for sustainable agriculture. With the increasing demand for eco-friendly and non-toxic agricultural practices, endophytic fungi present an attractive alternative to chemical pesticides and fertilizers. Further studies on these fungi will not only provide a better understanding of their interactions with host plants but also contribute to the development of sustainable agricultural practices and the discovery of novel bioactive compounds for various applications.

PJ and TM: conceptualization, editing, and supervision. TK and IC: literature review and drafting of original manuscript. AP, SP, and VK: writing and editing. All the authors have read and approved the final version of the manuscript.

IC was employed by Metropolis Healthcare Ltd.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.