Comparative Genome Mining Reveals Biosynthetic Potential of Endophytic Bacteria from Ethnomedicinal Plants of Manipur as Sustainable Natural Resources for Human Health Applications

Abstract

Background: Plants have always been a great source of medicine for us, and even with new ways of making drugs, they still are [1]. Some bacteria, called endophytic bacteria, live inside these plants and can make lots of different helpful chemicals for human health [2]. These chemicals are often similar to the ones the plants themselves make, or they can work well together with them. This is really interesting because it means these tiny living things can help us find new medicines. They can even make chemicals that are just like the ones the plants make, which is really useful. So, scientists are paying more attention to these interesting endophytic bacteria and the plants they live in, because they might hold the key to new and exciting medicines

Objectives: Recent breakthroughs in sequencing and mining microbial genomes have changed the way we discover special compounds, called metabolites, by letting us predict what a microbe can make before we even try to isolate it. Our research looks at five types of bacteria that live inside plants used in traditional medicine in the Indo-Myanmar Biodiversity Hotspot and to sequence their whole genome and report [3]. We want to see what kinds of useful compounds these bacteria can produce and if they can be a new, sustainable source of natural products for improving human health.

Methods: To understand how certain bacteria can help us, we looked at the complete DNA sequences of five special kinds of bacteria that live inside plants. We used various computer programs such as antiSMASH [4] and MIBiG [5] to find groups of genes that work together to make useful compounds. These compounds might be able to help people feel better. We compared the biosynthetic potential found in these bacteria to see what kinds of useful compounds they might make. We were looking at bacteria called Cellulosimicrobium cellulans MUKR5 [3], Enterobacter hormaechei ST4 Bacillus subtilis ST2, Bacillus paralicheniformis ST3, and Bacillus velezensis ST5. These bacteria were isolated from plants used in traditional medicine in Manipur which lies in the Indo Myanmar Biodiversity hot Spot region. We already had sequenced the whole genome of these bacteria earlier through Next Generation Seqencing and were interested to look at what useful things these bacteria could make to be used for human disease therapy.

Results: The process of comparative genome mining has revealed a stunning array of biosynthetic gene clusters, including non-ribosomal peptide synthetases, type I and type III polyketide synthases[6], ribosomally synthesized and post-translationally modified peptides, terpene biosynthetic pathways, siderophores, betalactones, thiopeptides, and hybrid PKS-NRPS clusters. One particular isolate, Bacillus velezensis ST5, stands out for its exceptionally rich biosynthetic architecture, boasting twelve predicted biosynthetic regions that encode a range of clinically relevant metabolites, such as difficidin, bacillaene, macrolactin H, surfactin, fengycin, bacilysin, and bacillibactin [8-18]. Meanwhile, other isolates have been found to possess complementary biosynthetic capabilities, encoding metabolites like enteromycin, alkylresorcinol, lankacidin C, aerobactin, bacitracin, lichenysin, pulcherriminic acid, and carbapenem-related compounds [19-27]. MIBiG analysis has also identified a multitude of biosynthetic core enzymes, tailoring enzymes, regulatory proteins, and transporter proteins that underpin the complex process of secondary metabolite biosynthesis. This diverse array of biosynthetic gene clusters and associated enzymes highlights the remarkable potential of these isolates to produce a wide range of valuable compounds.

Conclusion: In short, the study shows that bacteria living inside plants used in traditional medicine are a great source of new medicines. By looking at the genes of these bacteria, we can find new ways to make drugs to fight diseases. This is a powerful tool for finding new medicines and can help us make new treatments for many diseases, including ones that are hard to treat. These bacteria are like a treasure chest of new medicines, and studying them can help us discover new ways to fight diseases like cancer, infections, and more.