Issue 20, 2024

Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery

Abstract

Often referred to as the “second genome”, the human microbiome is at the epicenter of complex inter-habitat biochemical networks like the “gut–brain axis”, which has emerged as a significant determinant of cognition, overall health and well-being, as well as resistance to antibiotics and susceptibility to diseases. As part of a broader understanding of the nexus between the human microbiome, diseases and microbial interactions, whether encoded secondary metabolites (natural products) play crucial signalling roles has been the subject of intense scrutiny in the recent past. A major focus of these activities involves harvesting the genomic potential of the human microbiome via bioinformatics guided genome mining and culturomics. Through these efforts, an impressive number of structurally intriguing antibiotics, with enhanced chemical diversity vis-à-vis conventional antibiotics have been isolated from human commensal bacteria, thereby generating considerable interest in their total synthesis and expanding their therapeutic space for drug discovery. These developments augur well for the discovery of new drugs and antibiotics, particularly in the context of challenges posed by mycobacterial resistance and emerging new diseases. The current landscape of various synthetic campaigns and drug discovery initiatives on antibacterial natural products from the human microbiome is captured in this review with an intent to stimulate further activities in this interdisciplinary arena among the new generation.

Graphical abstract: Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery

Article information

Article type
Review Article
Submitted
14 Feb 2024
Accepted
19 Apr 2024
First published
19 Apr 2024

Org. Biomol. Chem., 2024,22, 4006-4030

Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery

S. Sengupta, S. Pabbaraja and G. Mehta, Org. Biomol. Chem., 2024, 22, 4006 DOI: 10.1039/D4OB00236A

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