Heterologous expression facilitates the discovery and characterization of marine microbial natural products

Abstract

Microbial natural products and their derivatives have been developed as a considerable part of clinical drugs and agricultural chemicals. Marine microbial natural products exhibit diverse chemical structures and bioactivities with substantial potential for the development of novel pharmaceuticals. However, discovering compounds with new skeletons from marine microbes remains challenging. In recent decades, multiple approaches have been developed to discover novel marine microbial natural products, among which heterologous expression has proven to be an effective method. Facilitated by large DNA cloning and comparative metabolomic technologies, a few novel bioactive natural products from marine microorganisms have been identified by the expression of their biosynthetic gene clusters (BGCs) in heterologous hosts. Heterologous expression is advantageous for characterizing gene functions and elucidating the biosynthetic mechanisms of natural products. This review provides an overview of recent progress in heterologous expression-guided discovery, biosynthetic mechanism elucidation, and yield optimization of natural products from marine microorganisms and discusses the future directions of the heterologous expression strategy in facilitating novel natural product exploitation.

Keywords

Marine natural products / Heterologous expression / Biosynthetic gene clusters / Biosynthetic mechanism

Declaration of AI in Scientific Writing

The authors declare no AI in scientific writing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Shuang Zhao: Writing - review & editing, Writing - original draft, Conceptualization. Ruiying Feng: Writing - review & editing, Writing - original draft, Conceptualization. Yuan Gu: Writing - review & editing, Writing - original draft, Conceptualization. Liyuan Han: Writing - review & editing. Xiaomei Cong: Writing - review & editing. Yang Liu: Writing - review & editing. Shuo Liu: Writing - review & editing. Qiyao Shen: Writing - review & editing. Liujie Huo: Writing - review & editing. Fu Yan: Writing - review & editing, Supervision, Conceptualization.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (82003639), Taishan Scholars Program of Shandong Province (tsqn201909049) and Qilu Youth Scholar Startup Funding of Shandong University.

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