Open AccessAn anaerobic bacterium host system for heterologous expression of natural product biosynthetic gene clusters
Author(s) -
Tingting Hao,
Zhoujie Xie,
Min Wang,
Liwei Liu,
Yuwei Zhang,
Weicang Wang,
Zhongwei Zhao,
Xuejin Zhao,
Pengwei Li,
Zhengyan Guo,
Shiqiang Gao,
Chunbo Lou,
Guodong Zhang,
Justin Merritt,
Geoff P. Horsman,
Yihua Chen
Publication year - 2019
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-019-11673-0
Subject(s) - heterologous expression , biology , heterologous , bacteria , gene , cloning (programming) , anaerobic bacteria , computational biology , microbiology and biotechnology , genetics , recombinant dna , computer science , programming language
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.