An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters

Tingting Hao, Zhoujie Xie, Min Wang, Liwei Liu, Yuwei Zhang, Weicang Wang, Zhao Zhang, Xuejin Zhao, Pengwei Li, Zhengyan Guo, Shushan Gao, Chunbo Lou, Guodong Zhang, Justin Merritt, Geoff P. Horsman and Yihua Chen ()
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Tingting Hao: Chinese Academy of Sciences
Zhoujie Xie: Chinese Academy of Sciences
Min Wang: Chinese Academy of Sciences
Liwei Liu: Chinese Academy of Sciences
Yuwei Zhang: Chinese Academy of Sciences
Weicang Wang: University of Massachusetts
Zhao Zhang: Chinese Academy of Sciences
Xuejin Zhao: Chinese Academy of Sciences
Pengwei Li: Chinese Academy of Sciences
Zhengyan Guo: Chinese Academy of Sciences
Shushan Gao: Chinese Academy of Sciences
Chunbo Lou: Chinese Academy of Sciences
Guodong Zhang: University of Massachusetts
Justin Merritt: Oregon Health & Science University
Geoff P. Horsman: Wilfrid Laurier University
Yihua Chen: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Anaerobic bacteria represent an overlooked rich source of biological and chemical diversity. Due to the challenge of cultivation and genetic intractability, assessing the capability of their biosynthetic gene clusters (BGCs) for secondary metabolite production requires an efficient heterologous expression system. However, this kind of host system is still unavailable. Here, we use the facultative anaerobe Streptococcus mutans UA159 as a heterologous host for the expression of BGCs from anaerobic bacteria. A natural competence based large DNA fragment cloning (NabLC) technique was developed, which can move DNA fragments up to 40-kb directly and integrate a 73.7-kb BGC to the genome of S. mutans UA159 via three rounds of NabLC cloning. Using this system, we identify an anti-infiltration compound, mutanocyclin, from undefined BGCs from human oral bacteria. We anticipate this host system will be useful for heterologous expression of BGCs from anaerobic bacteria.

Date: 2019
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DOI: 10.1038/s41467-019-11673-0

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