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Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line AMERICA
其他题名从基础代谢的酮糖中劫持羟基乙酰单元进入非核糖体聚肽装配线
Peng C(彭超); Pu JY(蒲津越); Song LQ(宋立强); Jian XH(蹇晓红); Tang MC(唐满成); Tang GL(唐功利)
2012
发表期刊Proc. Natl. Acad. Sci. U. S. A.
ISSN0027-8424
卷号109期号:22页码:8540-8545
摘要Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, alpha-ketoacids, and alpha-hydroxyacids originating from amino acid metabolism as well as polyketide-derived units can also be used by NRPS assembly lines as an alternative to amino acids. Ecteinascidin 743 (ET-743), naphthyridinomycin (NDM), and quinocarcin (QNC) are three important antitumor natural products belonging to the tetrahydroisoquinoline family. Although ET-743 has been approved as an anticancer drug, the origin of an identical two-carbon (C-2) fragment among these three antibiotics has not been elucidated despite much effort in the biosynthetic research in the past 30 y. Here we report that two unexpected two-component transketolases (TKases), NapB/NapD in the NDM biosynthetic pathway and QncN/QncL in QNC biosynthesis, catalyze the transfer of a glycolaldehyde unit from ketose to the lipoyl group to yield the glycolicacyl lipoic acid intermediate and then transfer the C-2 unit to an acyl carrier protein (ACP) to form glycolicacyl-S-ACP as an extender unit for NRPS. Our results demonstrate a unique NRPS extender unit directly derived from ketose phosphates through (alpha,beta-dihydroxyethyl)-thiamin diphosphate and a lipoyl group-tethered ester intermediate catalyzed by the TKase-ACP platform in the context of NDM and QNC biosynthesis, all of which also highlights the biosynthesis of ET-743. This hybrid system and precursor are distinct from the previously described universal modes involving the NRPS machinery. They exemplify an alternate strategy in hybrid NRPS biochemistry and enrich the diversity of precursors for NRPS combinatorial biosynthesis.
学科领域生命有机化学
部门归属中科院上海有机化学研究所
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收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/28525
专题生命有机化学国家重点实验室
通讯作者Tang GL(唐功利)
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GB/T 7714
Peng C,Pu JY,Song LQ,et al. Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line AMERICA[J]. Proc. Natl. Acad. Sci. U. S. A.,2012,109(22):8540-8545.
APA 彭超,蒲津越,宋立强,蹇晓红,唐满成,&唐功利.(2012).Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line AMERICA.Proc. Natl. Acad. Sci. U. S. A.,109(22),8540-8545.
MLA 彭超,et al."Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line AMERICA".Proc. Natl. Acad. Sci. U. S. A. 109.22(2012):8540-8545.
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