A metabologenomics strategy for rapid discovery of polyketides derived from modular polyketide synthases

被引:0
|
作者
Liu, Run-Zhou [1 ,2 ,3 ]
Zhang, Zhihan [2 ,3 ]
Li, Min [2 ,3 ]
Zhang, Lihan [2 ,3 ,4 ,5 ]
机构
[1] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China
[2] Westlake Univ, Sch Sci, Dept Chem, Key Lab Precise Synth Funct Mol Zhejiang Prov, Hangzhou 310030, Peoples R China
[3] Westlake Univ, Res Ctr Ind Future, Hangzhou 310030, Peoples R China
[4] Westlake Inst Adv Study, Inst Nat Sci, Hangzhou 310024, Peoples R China
[5] Westlake Lab Life Sci & Biomed, Hangzhou 310030, Peoples R China
基金
中国国家自然科学基金;
关键词
MASS-SPECTROMETRY; STRUCTURAL ELUCIDATION; GENOME; DEFECT; IDENTIFICATION; FRAGMENTATION; BIOSYNTHESIS; THIENAMYCIN; METABOLITES; FILTER;
D O I
暂无
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Bioinformatics-guided metabolomics is a powerful means for the discovery of novel natural products. However, the application of such metabologenomics approaches on microbial polyketides, a prominent class of natural products with diverse bioactivities, remains largely hindered due to our limited understanding on the mass spectrometry behaviors of these metabolites. Here, we present a metabologenomics approach for the targeted discovery of polyketides biosynthesized by modular type I polyketide synthases. We developed the NegMDF workflow, which uses mass defect filtering (MDF) supported by bioinformatic structural prediction, to connect the biosynthetic gene clusters to corresponding metabolite ions obtained under negative ionization mode. The efficiency of the NegMDF workflow is illustrated by rapid characterization of 22 polyketides synthesized by three gene clusters from a well-characterized strain Streptomyces cattleya NRRL 8057, including cattleyatetronates, new members of polyketides containing a rare tetronate moiety. Our results showcase the effectiveness of the MDF-based metabologenomics workflow for analyzing microbial natural products, and will accelerate the genome mining of microbial polyketides.
引用
收藏
页码:1696 / 1706
页数:12
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