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

TitleA Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters.
Publication TypeJournal Article
Year of Publication2021
AuthorsCovington, BC, Xu, F, Seyedsayamdost, MR
JournalAnnu Rev Biochem
Volume90
Pagination763-788
Date Published2021 06 20
ISSN1545-4509
KeywordsBacteria, Biological Products, Biosynthetic Pathways, Culture Techniques, Gene Expression Regulation, Multigene Family, Reverse Genetics
Abstract

<p>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.</p>

DOI10.1146/annurev-biochem-081420-102432
Alternate JournalAnnu Rev Biochem
PubMed ID33848426
PubMed Central IDPMC9148385
Grant ListR01 GM129496 / GM / NIGMS NIH HHS / United States