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
N1 - Funding Information:
We are grateful to Dr. Fengxia Qi from Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center for providing their Streptococcus mutans collections and for sharing the genetic information. We thank Dr. Jinwei Ren from IM, CAS for assistance in NMR analysis. This work was financially supported by the MOST of China (2018YFA0901901), the NNSF of China (31522001, 31570050), and the Key Research Program and the International Partnership Program of CAS (KFZD-SW-219, 153211KYSB20170014). Y.C. is a member of the “Hundred Talents Program” of CAS.
Publisher Copyright:
© 2019, The Author(s).
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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U2 - 10.1038/s41467-019-11673-0
DO - 10.1038/s41467-019-11673-0
M3 - Article
C2 - 31413323
AN - SCOPUS:85071047535
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3665
ER -