Insight into bicyclic thiopeptide biosynthesis benefited from development of a uniform approach for molecular engineering and production improvement

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	Insight into bicyclic thiopeptide biosynthesis benefited from development of a uniform approach for molecular engineering and production improvement
	Guo H(郭恒)1; Wang J(王绛)1; Li YM(李也名)1; Yu Y(虞沂)1; Zheng QF(郑庆飞)1; Wu JQ(吴杰群)1; Liu W(刘文)1
刊名	Chem. Sci.
	2014
卷号	5 期号:1 页码:240-246
其他题名	发展一种普适的用于分子改造和产量提高的方法以利于双环硫肽类抗生素生物合成机制的阐明
通讯作者	刘文
英文摘要	The ribosomal origin of thiopeptide antibiotics, a class of sulfur-rich and highly modified poly(thi)azolyl natural products, has recently been uncovered and features complex post-translational modifications (PTMs) of a precursor peptide. Based on molecular engineering and production improvement, we report insight into the biosynthesis of two bicyclic thiopeptide compounds, thiostrepton and nosiheptide. The PTMs of thiostrepton tolerate variations in the first two amino acids of the core peptide part of the precursor peptide: (1) the mutation of Ile1 to Val had no apparent effect on molecular maturation, suggesting that attachment of the quinaldic moiety at position 1 is not residue-dependent for the construction of the side ring system; and (2) the change of Ala2 to Ser led exclusively to the production of an analog that bears a corresponding dehydroamino acid residue, indicating that dehydration at position 2 is site-selective or that the oxazoline formed by cyclodehydration is inaccessible for maturation. For nosiheptide biosynthesis in particular, we provide the first structural evidence that construction of the specific side ring system precedes formation of the common central heterocycle domain and therefore propose that formation of a characteristic thiopeptide framework interweaves both common and specific PTMs that are interdependent. The above efforts benefited from the development of a uniform approach to examine the effectiveness for trans expression of gene encoding precursor peptides and associated PTM capacity. This approach is independent of knowledge regarding organism-specific regulatory mechanisms and potentially applicable to other systems that produce ribosomally synthesized peptide natural products.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1039/c3sc52015c
语种	英语
内容类型	期刊论文
源URL	[http://ir.sioc.ac.cn/handle/331003/38927]
专题	上海有机化学研究所_生命有机化学国家重点实验室
作者单位	1.中国科学院上海有机化学研究所, 生命有机化学国家重点实验室 2.湖州生物制造创新中心
推荐引用方式 GB/T 7714	Guo H,Wang J,Li YM,et al. Insight into bicyclic thiopeptide biosynthesis benefited from development of a uniform approach for molecular engineering and production improvement[J]. Chem. Sci.,2014,5(1):240-246.
APA	郭恒.,王绛.,李也名.,虞沂.,郑庆飞.,...&刘文.(2014).Insight into bicyclic thiopeptide biosynthesis benefited from development of a uniform approach for molecular engineering and production improvement.Chem. Sci.,5(1),240-246.
MLA	郭恒,et al."Insight into bicyclic thiopeptide biosynthesis benefited from development of a uniform approach for molecular engineering and production improvement".Chem. Sci. 5.1(2014):240-246.