Structural and Functional Analysis of Tetracenomycin F2 Cyclase from Streptomyces glaucescens

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Structural and functional analysis of tetracenomycin F2 cyclase from Streptomyces glaucescens. A type II polyketide cyclase.

Tetracenomycin F2 cyclase (tcmI gene product), catalyzes an aromatic rearrangement in the biosynthetic pathway for tetracenomycin C in Streptomyces glaucescens. The x-ray structure of this small enzyme has been determined to 1.9-A resolution together with an analysis of site-directed mutants of potential catalytic residues. The protein exhibits a dimeric betaalphabeta ferredoxin-like fold that ...

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

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 biosynthesi...

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Isolation of tetracenomycin C-nonproducing Streptomyces glaucescens mutants.

We analyzed the properties of tetracenomycin C (TcmC)-nonproducing mutants of Streptomyces glaucescens to establish the nature of pathway intermediates and to provide some information about the genetics of antitumor anthracycline antibiotic production. Using cosynthesis properties and metabolite accumulation data, we classified a collection of 34 TcmC-nonproducing strains into seven different g...

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Purification and characterization of the acyl carrier protein of the Streptomyces glaucescens tetracenomycin C polyketide synthase.

The acyl carrier protein (ACP) of the tetracenomycin C polyketide synthase, encoded by the tcmM gene, has been expressed in both Streptomyces glaucescens and Escherichia coli and purified to homogeneity. Expression of the tcmM gene in E. coli results mainly in the TcmM apo-ACP, whereas expression in S. glaucescens yields solely the holo-ACP. The purified holo-TcmM is active in a malonyl coenzym...

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Cyclase: Intramolecular Aldol Condensation in the Biosynthesis of Tetracenomycin C in Streptomyces gZaucescens7

Tetracenomycin (Tcm) F2 cyclase, which catalyzes the cyclization of the anthrone Tcm F2 to the naphthacenone Tcm F1 in the biosynthesis of the anthracycline antibiotic Tcm C in Streptomyces glaucescens, has been purified to homogeneity and characterized. The N-terminal sequence of the enzyme establishes that it is encoded by the tcml gene, whose deduced product has a molecular weight of 12 728....

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2004

ISSN: 0021-9258

DOI: 10.1074/jbc.m406144200