Abstract

The tremendous research outcomes have suggested that microbial ecology is a potent source of the candidate for drug discovery. Based on the findings of the omics technology studies on rhizospheric microbial diversity studies and plant-microbe interactions has led to several drug molecules. However, uncultured microbes have an excellent source for novel genes for drugs. Medicinal plants produce secondary metabolites with the influence of microbes both rhizospheric and endophytic microbes. The next-generation sequencing technologies such as amplicon sequencing, metagenomic sequencing, whole-genome sequencing and transcriptomic sequencing have significantly improved the biotechnological potentials of the rhizospheric microbiome of medicinal plants. In this chapter, we discuss recent works and challenges of rhizospheric microbial diversity, their evolution, the evolution of the research techniques and innovative combinations for drug discovery. Multiomics application and metagenomics approaches provide alternative strategies for herbal medicine productions and metabolic engineering for the production of secondary metabolites and novel lead molecules.

Introduction

Natural product discovery and its application in healing diseases increasing rapidly in the modern world. The importance of novel compounds from plants or natural origin is increasing significantly. There are three ways the isolation of novel compounds like ¨rational drug design¨,¨combinatorial chemistry and natural product discovery (Alvin et al,2014). Endophytes play an important role in natural product discovery. Endophytes are the microorganisms colonizing the inside healthy plant tissue at a particular time. Endophytes from medicinal plants responsible for the production of various compounds that show enormous bioactivities.

Metagenomics is a branch of science which is called community genomics and it involves genomic analysis of microbes by extracting DNA directly from the environment. The medicinal plant microbiome plays a significant role in natural product drug discovery in the recent drug discovery research. Metagenomics paves a correlated and holistic approach for finding metabolites and novel compounds from medicinal plants and endophytes. Metagenomics of plant-associated microbiome can predict species diversity, gene predictions and genomic assembly. Metagenomics can be structural, functional metagenomics, whole-genome metagenomics, targeted metagenomics. All these approaches can be used to analyze the microbiomes that are associated with medicinal plants and they can easily predict the role of microbes in regulating the secondary metabolite production in the medicinal plants. The main aim of this chapter is to describe how metagenomics approaches help in the bioprospecting of endophytes. it also describes a few recent developments leading to the production of novel bioactive and pharmaceutically important natural products from microbes and endophytes.

Drugs from medicinal plant microbiomes

Medicinal plants have unique structurally divergent bioactive compounds that are the results of specific associations with plant microbes’ interactions (Qi et al., 2012). Plant-based therapeutics from Mayans, aboriginal medicine of Australia, Ayurvedic of India, traditional medicines of China and several countries have reported more than 5,000 plant species being used for several diseases. These are referred to as the nature-based remedies that are utilized as effective treatment regimes. Many medicinal plants seem to be the basis for the drug discovery of many modern drugs as anti-infective, antibiotics, antimalarial and anticancer (Miller et al., 2012). In the past few decades, the research on plants with medicinal values are focused on their ingredients but now the trends are focused on their novel functions based on the chemical structures of medicinal plants’ microbiome. Research is continuously in progress that several natural molecules that are produced by plants can also be produced by plant microbiome (Gunatilaka, 2006). ,and medicinal plant-associated microbiome of this reported being a complex community as endophytes which are involved in the production of the same type of bioactive compounds. The complex community in interaction with the host referred to as endo-microbiome is involved indirectly and/or directly in the production of bioactive phytochemicals ( Miller et al., 2012). Natural products obtained from microbial communities are unusual chemical skeletons and diverse that can target varied regions to potential drug discovery. These attractive advantages of microbial natural products (MNPs) with an amalgamation of cutting edge for development in drug discovery that has gained the attention of several researchers. Hence, many reported MNPs have paved a way for novel drug leads. Several researchers from academics and industries have reported the actinomycetes from various geographical areas to assess the secondary metabolites production by high throughput screening HTS. The microbiome of Egyptian medicinal plants such as Matricaria chamomilla, Calendula officinalis and Solanum distichum grown in desert ecosystems showed the Gram-positive Bacillus spp which exhibited biocontrol and able to produce the plants’ flavonoids (Koberl et al., 2013). However, these are the culturable plant microbiomes that are reported which constitute around 1% of microbial communities . The deep research on the unculturable microbial community has suggested a wide diverse of chemicals and biological activities. The diverse uncultured microbial communities of various environmental conditions provide a novel repository category of natural products of economic importance. These untapped natural resources with recent advances in drug discovery could enable a novel class of antibiotics . MNPs libraries provide the basis for medicinal chemistry research to enhance the desired phenotype that can be targeted for drug discovery (Katz et al., 2016). From 1940 approximately 70,000 new MNPs have been described (Bérdy et al., 2012).

Future directions

Endophytes are very less studied in context to its role in synthesizing bioactive compounds that can be biological sources for novel lead molecule production. Biotransformation is useful for the production of active compounds. Endophytes can be used in the production of a pharmaceutically important novel compound from uncultured sources by using the genome mining and metagenomics approaches. (Gouda et al 2016). Metagenomics useful to find out more about the functional aspects of genes that are involved in secondary metabolite production. Production of bioactive compounds on a large scale is more important in the case of endophytes. Further studies on understanding the molecular mechanism of various metabolic pathways can enhance our understanding of metabolite production and set up industries for large scale production. (Fadiji and Babalola,2020). Metabolic engineering of targeted pathways and metabolic attenuations of bioactive compound synthesizing genes, downregulation of transcription factors for a particular gene and molecular mechanisms underlying the synthesis of bioactive compound sustainably can protect the environment(El-Sayed et al,2020)

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