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 | |
| State | Published - Dec 1 2019 |
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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 journal › Article
}
TY - JOUR
T1 - An anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters
AU - Hao, Tingting
AU - Xie, Zhoujie
AU - Wang, Min
AU - Liu, Liwei
AU - Zhang, Yuwei
AU - Wang, Weicang
AU - Zhang, Zhao
AU - Zhao, Xuejin
AU - Li, Pengwei
AU - Guo, Zhengyan
AU - Gao, Shushan
AU - Lou, Chunbo
AU - Zhang, Guodong
AU - Merritt, Justin
AU - Horsman, Geoff P.
AU - Chen, Yihua
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85071047535&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-11673-0
DO - 10.1038/s41467-019-11673-0
M3 - Article
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3665
ER -