A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters

Overview

Journal Annu Rev Biochem

Publisher Annual Reviews

Specialty Biochemistry

Date 2021 Apr 13

PMID 33848426

Citations 44

Authors

Brett C Covington

Fei Xu

Mohammad R Seyedsayamdost

Affiliations

Soon will be listed here.

Abstract

Microbial natural products have provided an important source of therapeutic leads and motivated research and innovation in diverse scientific disciplines. In recent years, it has become evident that bacteria harbor a large, hidden reservoir of potential natural products in the form of silent or cryptic biosynthetic gene clusters (BGCs). These can be readily identified in microbial genome sequences but do not give rise to detectable levels of a natural product. Herein, we provide a useful organizational framework for the various methods that have been implemented for interrogating silent BGCs. We divide all available approaches into four categories. The first three are endogenous strategies that utilize the native host in conjunction with classical genetics, chemical genetics, or different culture modalities. The last category comprises expression of the entire BGC in a heterologous host. For each category, we describe the rationale, recent applications, and associated advantages and limitations.

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