Establishment of recombineering genome editing system in Paraburkholderia megapolitana empowers activation of silent biosynthetic gene clusters

Establishment of recombineering genome editing system in Paraburkholderia megapolitana empowers activation of silent biosynthetic gene clusters
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Paraburkholderia megapolitana重组工程基因组编辑系统的建立能够激活沉默的生物合成基因簇。

DOI:
10.1111/1751-7915.13535
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发表时间:
2020-03-01
影响因子:
5.7
通讯作者:
Bian, Xiaoying
Bian, Xiaoying
中科院分区:
工程技术2区
文献类型:
--
作者:
Zheng, Wentao;Wang, Xue;Bian, Xiaoying

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The Burkholderiales are an emerging source of bioactive natural products. Their genomes contain a large number of cryptic biosynthetic gene clusters (BGCs), indicating great potential for novel structures. However, the lack of genetic tools for the most of Burkholderiales strains restricts the mining of these cryptic BGCs. We previously discovered novel phage recombinases Red alpha beta 7029 from Burkholderiales strain DSM 7029 that could help in efficiently editing several Burkholderiales genomes and established the recombineering genome editing system in Burkholderialse species. Herein, we report the application of this phage recombinase system in another species Paraburkholderia megapolitana DSM 23488, resulting in activation of two silent non-ribosomal peptide synthetase/polyketide synthase BGCs. A novel class of lipopeptide, haereomegapolitanin, was identified through spectroscopic characterization. Haereomegapolitanin A represents an unusual threonine-tagged lipopeptide which is longer than the predicted NRPS assembly line. This recombineering-mediated genome editing system shows great potential for genetic manipulation of more Burkholderiales species to activate silent BGCs for bioactive metabolites discovery.