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

Publication Year
2021

Type

Journal Article
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.

Journal
Annu Rev Biochem
Volume
90
Pages
763-788
Date Published
2021 Jun 20
ISSN Number
1545-4509
Alternate Journal
Annu Rev Biochem
PMCID
PMC9148385
PMID
33848426