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Analysis of YM-216391 Biosynthetic Gene Cluster and Improvement of the Cyclopeptide Production in Heterologous Host
Jian XH; Pan HX; Ning TT; Shi YY; Chen YS; Li Y; Zeng XW; Xu J; Tang GL
2012
Source PublicationACS Chem Biol
Issue1
Abstract

YM-216391, an antitumor natural product, represents a new class of cyclic peptides containing a polyoxazolethiazole moiety. Herein we describe its gene cluster encoding the biosynthetic paradigm featuring a ribosomally synthesizing precursor peptide followed by a series of novel posttranslational modifications, which include (i) cleavage of both N-terminal leader peptide and C-terminal extension peptide and cyclization in a head-to-tail fashion, (ii) conversion of an L-Ile to D-allo-Ile, and (iii) β-hydroxylation of Phe by a P450 monooxygenase followed by further heterocyclization and oxidation to form a phenyloxazole moiety. The cluster was heterologously expressed in Streptomyces lividans to bypass difficult genetic manipulation. Deletion of the ymR3 gene, encoding a putative transcriptional regulator, increased the YM-216391 yield about 20-fold higher than the original yields for the heterologous expression of wild-type cluster, which set the stage for further combinatorial biosynthesis.

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YM-216391, an antitumor natural product, represents a new class of cyclic peptides containing a polyoxazolethiazole moiety. Herein we describe its gene cluster encoding the biosynthetic paradigm featuring a ribosomally synthesizing precursor peptide followed by a series of novel posttranslational modifications, which include (i) cleavage of both N-terminal leader peptide and C-terminal extension peptide and cyclization in a head-to-tail fashion, (ii) conversion of an L-Ile to D-allo-Ile, and (iii) β-hydroxylation of Phe by a P450 monooxygenase followed by further heterocyclization and oxidation to form a phenyloxazole moiety. The cluster was heterologously expressed in Streptomyces lividans to bypass difficult genetic manipulation. Deletion of the ymR3 gene, encoding a putative transcriptional regulator, increased the YM-216391 yield about 20-fold higher than the original yields for the heterologous expression of wild-type cluster, which set the stage for further combinatorial biosynthesis.

KeywordAnalysis Of Ym-216391 BiosynThetic Gene Cluster And Improvement Of The Cyclopeptide Production In Heterologous Host
Subject Area功能基因组
Document Type期刊论文
Identifierhttp://ir.qibebt.ac.cn/handle/337004/965
Collection单细胞中心组群
Recommended Citation
GB/T 7714
Jian XH,Pan HX,Ning TT,et al. Analysis of YM-216391 Biosynthetic Gene Cluster and Improvement of the Cyclopeptide Production in Heterologous Host[J]. ACS Chem Biol,2012(1).
APA Jian XH.,Pan HX.,Ning TT.,Shi YY.,Chen YS.,...&Tang GL.(2012).Analysis of YM-216391 Biosynthetic Gene Cluster and Improvement of the Cyclopeptide Production in Heterologous Host.ACS Chem Biol(1).
MLA Jian XH,et al."Analysis of YM-216391 Biosynthetic Gene Cluster and Improvement of the Cyclopeptide Production in Heterologous Host".ACS Chem Biol .1(2012).
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