Challenges and Advances in Genome Editing Technologies in <i>Streptomyces</i>

The genome of <i>Streptomyces</i> encodes a high number of natural product (NP) biosynthetic gene clusters (BGCs). Most of these BGCs are not expressed or are poorly expressed (commonly called silent BGCs) under traditional laboratory experimental conditions. These NP BGCs represent an u...

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Bibliographic Details
Main Authors: Yawei Zhao, Guoquan Li, Yunliang Chen, Yinhua Lu
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/10/5/734
Description
Summary:The genome of <i>Streptomyces</i> encodes a high number of natural product (NP) biosynthetic gene clusters (BGCs). Most of these BGCs are not expressed or are poorly expressed (commonly called silent BGCs) under traditional laboratory experimental conditions. These NP BGCs represent an unexplored rich reservoir of natural compounds, which can be used to discover novel chemical compounds. To activate silent BGCs for NP discovery, two main strategies, including the induction of BGCs expression in native hosts and heterologous expression of BGCs in surrogate <i>Streptomyces</i> hosts, have been adopted, which normally requires genetic manipulation. So far, various genome editing technologies have been developed, which has markedly facilitated the activation of BGCs and NP overproduction in their native hosts, as well as in heterologous <i>Streptomyces</i> hosts. In this review, we summarize the challenges and recent advances in genome editing tools for <i>Streptomyces</i> genetic manipulation with a focus on editing tools based on clustered regularly interspaced short palindrome repeat (CRISPR)/CRISPR-associated protein (Cas) systems. Additionally, we discuss the future research focus, especially the development of endogenous CRISPR/Cas-based genome editing technologies in <i>Streptomyces</i>.
ISSN:2218-273X