Ablation of the otcC Gene Encoding a Post-polyketide Hydroxylase from the Oxytetracyline Biosynthetic Pathway in Streptomyces rimosus Results in Novel Polyketides with Altered Chain Length

Peric-Concha, N., Borovička, B., Long, P.F., Hranueli, D., Waterman, P.G. and Hunter, I.S. (2005) Ablation of the otcC Gene Encoding a Post-polyketide Hydroxylase from the Oxytetracyline Biosynthetic Pathway in Streptomyces rimosus Results in Novel Polyketides with Altered Chain Length. Journal of Biological Chemistry, 280 (45). pp. 37455-37460. 10.1074/jbc.M503191200.

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DOI: 10.1074/jbc.M503191200

Abstract

Oxytetracycline (OTC) is a 19-carbon polyketide antibiotic made by Streptomyces rimosus. The otcC gene encodes an anhydrotetracycline oxygenase that catalyzes a hydroxylation of the anthracycline structure at position C-6 after biosynthesis of the polyketide backbone is completed. A recombinant strain of S. rimosus that was disrupted in the genomic copy of otcC synthesized a novel C-17 polyketide. This result indicates that the absence of the otcC gene product significantly influences the ability of the OTC “minimal” polyketide synthase to make a polyketide product of the correct chain length. A mutant copy of otcC was made by site-directed mutagenesis of three essential glycine codons located within the putative NADPH-binding domain. The mutant gene was expressed in Escherichia coli, and biochemical analysis confirmed that the gene product was catalytically inactive. When the mutant gene replaced the ablated gene in the chromosome of S. rimosus, the ability to make a 19-carbon backbone was restored, indicating that OtcC is an essential partner in the quaternary structure of the synthase complex.

Item Type:Article
Departments, units and centres:Department of Pharmaceutics > Department of Pharmaceutics
ID Code:3213
Journal or Publication Title:Journal of Biological Chemistry
Deposited By:Library Staff
Deposited On:11 May 2012 17:15
Last Modified:11 May 2012 17:15

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