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四环素霉素F2和四环素霉素F1的分离与结构解析:浅绿链霉菌中四环素霉素C生物合成的早期中间体

Isolation and structural elucidation of tetracenomycin F2 and tetracenomycin F1: early intermediates in the biosynthesis of tetracenomycin C in Streptomyces glaucescens.

作者信息

Shen B, Nakayama H, Hutchinson C R

机构信息

School of Pharmacy, University of Wisconsin, Madison 53706.

出版信息

J Nat Prod. 1993 Aug;56(8):1288-93. doi: 10.1021/np50098a013.

DOI:10.1021/np50098a013
PMID:8229013
Abstract

This report describes the fermentation, isolation, and structural elucidation of tetracenomycin (Tcm) F2 [2], a metabolite produced by a blocked mutant strain WMH1092 of the Tcm C [1] producer Streptomyces glaucescens and by the recombinant strain S. glaucescens WMH1077 (pWHM722). Elucidation of the Tcm F2 structure shows that 2 is the earliest intermediate identified to date in the biosynthesis of 1. This is supported by the fact that 2 is very efficiently biotransformed to 1 by the S. glaucescens WMH1068 strain and is enzymatically converted to Tcm F1 [3] and to Tcm D3 [4], a known intermediate of Tcm C biosynthesis.

摘要

本报告描述了四环素霉素(Tcm)F2 [2] 的发酵、分离及结构解析,Tcm F2是由Tcm C [1] 产生菌蓝灰色链霉菌的阻断突变株WMH1092以及重组菌株蓝灰色链霉菌WMH1077(pWHM722)产生的一种代谢产物。Tcm F2结构的解析表明,化合物2是迄今为止在1的生物合成中鉴定出的最早中间体。这一点得到了以下事实的支持:化合物2能被蓝灰色链霉菌WMH1068菌株高效地生物转化为1,并能被酶促转化为Tcm F1 [3] 和Tcm D3 [4],Tcm D3是Tcm C生物合成的一个已知中间体。

相似文献

1
Isolation and structural elucidation of tetracenomycin F2 and tetracenomycin F1: early intermediates in the biosynthesis of tetracenomycin C in Streptomyces glaucescens.四环素霉素F2和四环素霉素F1的分离与结构解析:浅绿链霉菌中四环素霉素C生物合成的早期中间体
J Nat Prod. 1993 Aug;56(8):1288-93. doi: 10.1021/np50098a013.
2
The tcmVI region of the tetracenomycin C biosynthetic gene cluster of Streptomyces glaucescens encodes the tetracenomycin F1 monooxygenase, tetracenomycin F2 cyclase, and, most likely, a second cyclase.浅青紫链霉菌的四环素霉素C生物合成基因簇的tcmVI区域编码四环素霉素F1单加氧酶、四环素霉素F2环化酶,以及极有可能的第二种环化酶。
J Bacteriol. 1993 Dec;175(23):7571-80. doi: 10.1128/jb.175.23.7571-7580.1993.
3
Tetracenomycin F2 cyclase: intramolecular aldol condensation in the biosynthesis of tetracenomycin C in Streptomyces glaucescens.四环素霉素F2环化酶:在浅绿链霉菌中四环素霉素C生物合成过程中的分子内羟醛缩合反应。
Biochemistry. 1993 Oct 19;32(41):11149-54. doi: 10.1021/bi00092a026.
4
Triple hydroxylation of tetracenomycin A2 to tetracenomycin C in Streptomyces glaucescens. Overexpression of the tcmG gene in Streptomyces lividans and characterization of the tetracenomycin A2 oxygenase.在浅青紫链霉菌中四环霉素A2三重羟基化生成四环霉素C。天蓝色链霉菌中tcmG基因的过表达及四环霉素A2加氧酶的特性分析。
J Biol Chem. 1994 Dec 2;269(48):30726-33.
5
Tetracenomycin F1 monooxygenase: oxidation of a naphthacenone to a naphthacenequinone in the biosynthesis of tetracenomycin C in Streptomyces glaucescens.四环素霉素F1单加氧酶:在青灰色链霉菌中四环素霉素C生物合成过程中,将萘并蒽酮氧化为萘并蒽醌。
Biochemistry. 1993 Jul 6;32(26):6656-63. doi: 10.1021/bi00077a019.
6
Metabolic products of microorganisms. 249. Tetracenomycins B3 and D3, key intermediates of the elloramycin and tetracenomycin C biosynthesis.微生物的代谢产物。249. 四并萘霉素B3和D3,埃罗霉素和四并萘霉素C生物合成的关键中间体。
J Antibiot (Tokyo). 1988 Aug;41(8):1066-73. doi: 10.7164/antibiotics.41.1066.
7
Overproduction of the acyl carrier protein component of a type II polyketide synthase stimulates production of tetracenomycin biosynthetic intermediates in Streptomyces glaucescens.II型聚酮合酶酰基载体蛋白组分的过量产生刺激了浅青紫链霉菌中四环素霉素生物合成中间体的产生。
J Antibiot (Tokyo). 1994 Jan;47(1):54-63. doi: 10.7164/antibiotics.47.54.
8
Anthracycline metabolites of tetracenomycin C-nonproducing Streptomyces glaucescens mutants.淡青链霉菌四环霉素C非产生菌突变体的蒽环类代谢产物。
J Bacteriol. 1986 Aug;167(2):581-6. doi: 10.1128/jb.167.2.581-586.1986.
9
Cloning and heterologous expression of a gene cluster for the biosynthesis of tetracenomycin C, the anthracycline antitumor antibiotic of Streptomyces glaucescens.青灰链霉菌蒽环类抗肿瘤抗生素四环素霉素C生物合成基因簇的克隆与异源表达
Proc Natl Acad Sci U S A. 1987 Jul;84(13):4445-9. doi: 10.1073/pnas.84.13.4445.
10
Transcriptional analysis of the Streptomyces glaucescens tetracenomycin C biosynthesis gene cluster.浅绿链霉菌四环素霉素C生物合成基因簇的转录分析
J Bacteriol. 1993 Jun;175(12):3887-92. doi: 10.1128/jb.175.12.3887-3892.1993.

引用本文的文献

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Identification of a monooxygenase from Streptomyces coelicolor A3(2) involved in biosynthesis of actinorhodin: purification and characterization of the recombinant enzyme.来自天蓝色链霉菌A3(2)的参与放线紫红素生物合成的单加氧酶的鉴定:重组酶的纯化与表征
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Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6600-4. doi: 10.1073/pnas.93.13.6600.
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The tcmVI region of the tetracenomycin C biosynthetic gene cluster of Streptomyces glaucescens encodes the tetracenomycin F1 monooxygenase, tetracenomycin F2 cyclase, and, most likely, a second cyclase.浅青紫链霉菌的四环素霉素C生物合成基因簇的tcmVI区域编码四环素霉素F1单加氧酶、四环素霉素F2环化酶,以及极有可能的第二种环化酶。
J Bacteriol. 1993 Dec;175(23):7571-80. doi: 10.1128/jb.175.23.7571-7580.1993.
5
Engineered biosynthesis of novel polyketides: influence of a downstream enzyme on the catalytic specificity of a minimal aromatic polyketide synthase.新型聚酮化合物的工程化生物合成:一种下游酶对最小芳香族聚酮合酶催化特异性的影响
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11542-6. doi: 10.1073/pnas.91.24.11542.
6
Functional analysis of putative beta-ketoacyl:acyl carrier protein synthase and acyltransferase active site motifs in a type II polyketide synthase of Streptomyces glaucescens.浅青紫链霉菌II型聚酮合酶中假定的β-酮酰基:酰基载体蛋白合酶和酰基转移酶活性位点基序的功能分析
J Bacteriol. 1995 Jan;177(2):477-81. doi: 10.1128/jb.177.2.477-481.1995.