Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines

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	Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines
	Zhu, YG; Huang, CS; Yang, CF; Zhang, WJ; Zhang, LP; De, BC; Jiang, XD; Fang, CY; Zhang, QB; Yuan, CS
刊名	NATURE COMMUNICATIONS
	2018
卷号	9 页码:-2088
通讯作者	h.w.liu@mail.utexas.edu ; czhang2006@gmail.com
英文摘要	Lomaiviticin A and difluostatin A are benzofluorene-containing aromatic polyketides in the atypical angucycline family. Although these dimeric compounds are potent antitumor agents, how nature constructs their complex structures remains poorly understood. Herein, we report the discovery of a number of fluostatin type dimeric aromatic polyketides with varied C-C and C-N coupling patterns. We also demonstrate that these dimers are not true secondary metabolites, but are instead derived from non-enzymatic deacylation of biosynthetic acyl fluostatins. The non-enzymatic deacylation proceeds via a transient quinone methide like intermediate which facilitates the subsequent C-C/C-N coupled dimerization. Characterization of this unusual property of acyl fluostatins explains how dimerization takes place, and suggests a strategy for the assembly of C-C and C-N coupled aromatic polyketide dimers. Additionally, a deacylase FlsH was identified which may help to prevent accumulation of toxic quinone methides by catalyzing hydrolysis of the acyl group.
学科主题	Science & Technology - Other Topics
内容类型	期刊论文
源URL	[http://ir.scsio.ac.cn/handle/344004/16945]
专题	南海海洋研究所_中科院海洋生物资源可持续利用重点实验室
推荐引用方式 GB/T 7714	Zhu, YG,Huang, CS,Yang, CF,et al. Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines[J]. NATURE COMMUNICATIONS,2018,9:-2088.
APA	Zhu, YG.,Huang, CS.,Yang, CF.,Zhang, WJ.,Zhang, LP.,...&Zhang, CS.(2018).Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines.NATURE COMMUNICATIONS,9,-2088.
MLA	Zhu, YG,et al."Molecular basis of dimer formation during the biosynthesis of benzofluorene-containing atypical angucyclines".NATURE COMMUNICATIONS 9(2018):-2088.