Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics

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	Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics
	Fang J(方洁) ; Zhang YP(张宜平) ; Huang LJ(黄丽娟) ; Jia XY(贾新颖) ; Zhang Q(张琪) ; Zhang X(张序) ; Tang GL(唐功利) ; Liu W(刘文)
刊名	J. Bacteriol.
	2008
卷号	190 期号:17 页码:6014-6025
ISSN号	0021-9193
其他题名	Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics
通讯作者	刘文
英文摘要	Tetrocarcin A (TCA), produced by Micromonospora chalcea NRRL 11289, is a spirotetronate antibiotic with potent antitumor activity and versatile modes of action. In this study, the biosynthetic gene cluster of TCA was cloned and localized to a 108-kb contiguous DNA region. In silico sequence analysis revealed 36 putative genes that constitute this cluster (including 11 for unusual sugar biosynthesis, 13 for aglycone formation, and 4 for glycosylations) and allowed us to propose the biosynthetic pathway of TCA. The formation of D-tetronitrose, L-amicetose, and L-digitoxose may begin with D-glucose-1-phosphate, share early enzymatic steps, and branch into different pathways by competitive actions of specific enzymes. Tetronolide biosynthesis involves the incorporation of a 3-C unit with a polyketide intermediate to form the characteristic spirotetronate moiety and trans-decalin system. Further substitution of tetronolide with five deoxysugars (one being a deoxynitrosugar) was likely due to the activities of four glycosyltransferases. In vitro characterization of the first enzymatic step by utilization of 1,3-biphosphoglycerate as the substrate and in vivo cross-complementation of the bifunctional fused gene tcaD3 (with the functions of chlD3 and chlD4) to Delta chlD3 and Delta chlD4 in chlorothricin biosynthesis supported the highly conserved tetronate biosynthetic strategy in the spirotetronate family. Deletion of a large DNA fragment encoding polyketide synthases resulted in a non-TCA-producing strain, providing a clear background for the identification of novel analogs. These findings provide insights into spirotetronate biosynthesis and demonstrate that combinatorial-biosynthesis methods can be applied to the TCA biosynthetic machinery to generate structural diversity.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1128/JB.00533-08
语种	英语
WOS记录号	WOS:000258695400031
公开日期	2013-08-14
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/27707]
专题	上海有机化学研究所_上海有机化学研究所
推荐引用方式 GB/T 7714	Fang J,Zhang YP,Huang LJ,et al. Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics[J]. J. Bacteriol.,2008,190(17):6014-6025.
APA	方洁.,张宜平.,黄丽娟.,贾新颖.,张琪.,...&刘文.(2008).Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics.J. Bacteriol.,190(17),6014-6025.
MLA	方洁,et al."Cloning and characterization of the tetrocarcin a gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics".J. Bacteriol. 190.17(2008):6014-6025.