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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article number3665
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Anaerobic Bacteria
Multigene Family
Biological Products
genes
bacteria
Bacteria
Genes
products
Streptococcus mutans
Cloning
Organism Cloning
anaerobes
deoxyribonucleic acid
fragments
streptococcus
biological diversity
genome
metabolites
Biodiversity
DNA

ASJC Scopus subject areas

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

Cite this

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 journalArticle

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, GP & Chen, Y 2019, 'An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters', Nature communications, vol. 10, no. 1, 3665. https://doi.org/10.1038/s41467-019-11673-0
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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