Title | A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Covington, BC, Xu, F, Seyedsayamdost, MR |
Journal | Annu Rev Biochem |
Volume | 90 |
Pagination | 763-788 |
Date Published | 2021 06 20 |
ISSN | 1545-4509 |
Keywords | Bacteria, 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> |
DOI | 10.1146/annurev-biochem-081420-102432 |
Alternate Journal | Annu Rev Biochem |
PubMed ID | 33848426 |
PubMed Central ID | PMC9148385 |
Grant List | R01 GM129496 / GM / NIGMS NIH HHS / United States |