HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thamchaipenet, A. Articles by Hunter, I. S. Search for Related Content PubMed PubMed Citation Articles by Thamchaipenet, A. Articles by Hunter, I. S. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 46, 32829-32834, November 12, 1999

Disruption of an Aromatase/Cyclase from the Oxytetracycline Gene Cluster of Streptomyces rimosus Results in Production of Novel Polyketides with Shorter Chain Lengths

Hrvoje Petkovi^§, Arinthip Thamchaipenet^¶, Li-Hong Zhou, Daslav Hranueli, Peter Raspor^§, Peter G. Waterman, and Iain S. Hunter

From the  Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, Scotland G1 1XW, United Kingdom, ^§ Biotechnical Faculty, University of Ljubljana, Ljubljana, 61000 Slovenia, ^¶ Department of Genetics, Kasetsart University, Bangkok, 10900 Thailand, and  PLIVA d.d., Research Institute, Anti-infective Research, 10000 Zagreb, Croatia

Oxytetracycline is a polyketide antibiotic made by Streptomyces rimosus. From DNA sequencing, the gene product of otcD1 is deduced to function as a bifunctional cyclase/aromatase involved in ring closure of the polyketide backbone. Although otcD1 is contiguous with the ketoreductase gene, they are located an unusually large distance from the genes encoding the "minimal polyketide synthase" of the oxytetracycline gene cluster. A recombinant, disrupted in the genomic copy of otcD1, made four novel polyketides, all of shorter chain length (by up to 10 carbons) than oxytetracycline. All four novel structures contained the unusual carboxamido group, typical of oxytetracycline. This implies that the carboxamido group is present at the start of biosynthesis of oxytetracycline, a topic that has been debated in the literature. Loss of the cyclase protein has a profound influence on the length of polyketide chain assembled, implying that OtcD1 plays a greater role in the overall integrity of the quaternary structure of the polyketide complex than hitherto imagined.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				W. Zhang, K. Watanabe, C. C. C. Wang, and Y. Tang Investigation of Early Tailoring Reactions in the Oxytetracycline Biosynthetic Pathway J. Biol. Chem., August 31, 2007; 282(35): 25717 - 25725. [Abstract] [Full Text] [PDF]

				H. Petkovic, J. Cullum, D. Hranueli, I. S. Hunter, N. Peric-Concha, J. Pigac, A. Thamchaipenet, D. Vujaklija, and P. F. Long Genetics of Streptomyces rimosus, the Oxytetracycline Producer Microbiol. Mol. Biol. Rev., September 1, 2006; 70(3): 704 - 728. [Abstract] [Full Text] [PDF]

				W. Zhang, B. D. Ames, S.-C. Tsai, and Y. Tang Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase Appl. Envir. Microbiol., April 1, 2006; 72(4): 2573 - 2580. [Abstract] [Full Text] [PDF]

				N. Peric-Concha, B. Borovicka, P. F. Long, D. Hranueli, P. G. Waterman, and I. S. Hunter 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 J. Biol. Chem., November 11, 2005; 280(45): 37455 - 37460. [Abstract] [Full Text] [PDF]