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; Yihua Chen

doi:10.1038/s41467-019-11673-0

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, Yihua Chen

School of Dentistry

Research output: Contribution to journal › Article

6 Scopus citations

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.

Original language	English (US)
Article number	3665
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11673-0
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Hao, T., Xie, Z., Wang, M., Liu, L., Zhang, Y., Wang, W., Zhang, Z., Zhao, X., Li, P., Guo, Z., Gao, S., Lou, C., Zhang, G., Merritt, J., Horsman, G. P., & Chen, Y. (2019). An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters. Nature communications, 10(1), [3665]. https://doi.org/10.1038/s41467-019-11673-0

An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters. / Hao, Tingting; Xie, Zhoujie; Wang, Min; Liu, Liwei; Zhang, Yuwei; Wang, Weicang; Zhang, Zhao; Zhao, Xuejin; Li, Pengwei; Guo, Zhengyan; Gao, Shushan; Lou, Chunbo; Zhang, Guodong; Merritt, Justin; Horsman, Geoff P.; Chen, Yihua.

In: Nature communications, Vol. 10, No. 1, 3665, 01.12.2019.

Research output: Contribution to journal › Article

Hao, Tingting ; Xie, Zhoujie ; Wang, Min ; Liu, Liwei ; Zhang, Yuwei ; Wang, Weicang ; Zhang, Zhao ; Zhao, Xuejin ; Li, Pengwei ; Guo, Zhengyan ; Gao, Shushan ; Lou, Chunbo ; Zhang, Guodong ; Merritt, Justin ; Horsman, Geoff P. ; Chen, Yihua. / An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters. In: Nature communications. 2019 ; Vol. 10, No. 1.

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