Abstract

Marine microorganisms have proven to be a source of new natural products with a wide spectrum of biological activities relevant in different industrial sectors. The ever-increasing number of sequenced microbial genomes has highlighted a discrepancy between the number of gene clusters potentially encoding the production of natural products and the actual number of chemically characterized metabolites for a given microorganism. Homologous and heterologous expression of these biosynthetic genes, which are often silent under experimental laboratory culture conditions, may lead to the discovery of new cryptic natural products of medical and biotechnological interest. Several new genetic and cultivation-based strategies have been developed to meet this challenge. The OSMAC approach (one strain—many compounds), based on modification of growth conditions, has proven to be a powerful strategy for the discovery of new cryptic natural products. As a direct extension of this approach, the addition of chemical elicitors or epigenetic modifiers have also been used to activate silent genes. This review looks at the structures and biological activities of new cryptic metabolites from marine-derived microorganisms obtained using the OSMAC approach, the addition of chemical elicitors, and enzymatic inhibitors and epigenetic modifiers. It covers works published up to June 2021.

Highlights

  • This review focuses on the chemical structures and biological activities of new cryptic metabolites from marine-derived microorganisms obtained using the One Strain—Many Compounds” (OSMAC) approach, the addition of chemical elicitors, enzymatic inhibitors and epigenetic modifiers

  • Vorinostat (SAHA) added to the culture medium led to the isolation of a new naturally occurring diketopiperazine derivative, 3-[6-(2-methylpropyl)2-oxo-1H-pyrazin-3-yl]propanamide (106), and (+)- and (−)-brevianamide X (107, 108), which were exclusively observed in the presence of the epigenetic modifier

  • Microorganisms produce a wide variety of compounds with this chemical skeleton and a growing number have been isolated from marine microorganisms over the last decade, making this a potential source of polyketides with new structures and interesting activity

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Some chemicals such as metyrapone, tricyclazole and jasplakinolide can selectively inhibit the activity of monooxygenase and hydrolase in the biosynthetic pathway and promote the progress of other metabolic pathways [35,36]. Another extension of the cultivation-dependent approach is epigenetic activation which entails adding chemicals to the culture medium that can modulate gene expression. This review focuses on the chemical structures and biological activities of new cryptic metabolites from marine-derived microorganisms obtained using the OSMAC approach, the addition of chemical elicitors, enzymatic inhibitors and epigenetic modifiers.

Alkaloids
OSMAC Approach
Epigenetic Approach
Peptides
Polyketides
Findings
Conclusions
Full Text
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