This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Summers, R G Articles by Hutchinson, C R Search for Related Content PubMed PubMed Citation Articles by Summers, R G Articles by Hutchinson, C R

research-article

Nucleotide sequence of the tcmII-tcmIV region of the tetracenomycin C biosynthetic gene cluster of Streptomyces glaucescens and evidence that the tcmN gene encodes a multifunctional cyclase-dehydratase-O-methyl transferase.

School of Pharmacy, University of Wisconsin-Madison 53706.

ABSTRACT

Mutations in the tcmII-tcmIV region of the Streptomyces glaucescens chromosome block the C-3 and C-8 O-methylations of the polyketide antibiotic tetracenomycin C (Tcm C). The nucleotide sequence of this region reveals the presence of two genes, tcmN and tcmO, whose deduced protein products display similarity to the hydroxyindole O-methyl transferase of the bovine pineal gland, an enzyme that catalyzes a phenolic O-methylation analogous to those required for the biosynthesis of Tcm C. The deduced product of the tcmN gene also has an N-terminal domain that shows similarity to the putative ActVII and WhiE ORFVI proteins of Streptomyces coelicolor. The tcmN N-terminal domain can be separated from the remainder of the tcmN gene product, and when coupled on a plasmid with the Tcm C polyketide synthase genes (tcmKLM), this domain enables high-level production of an early, partially cyclized intermediate of Tcm C in a Tcm C- null mutant or in a heterologous host (Streptomyces lividans). By analogy to fatty acid biosynthesis, the tcmKLM polyketide synthase gene products are probably sufficient to produce the linear decaketide precursor of Tcm C; thus, the tcmN N-terminal domain is most likely responsible for one or more of the early cyclizations and, perhaps, the attendant dehydrations that lead to the partially cyclized intermediate. The tcmN gene therefore appears to encode a multifunctional cyclase-dehydratase-3-O-methyl transferase. The tcmO gene encodes the 8-O-methyl transferase.

This article has been cited by other articles:

• Ramos, A., Lombo, F., Brana, A. F., Rohr, J., Mendez, C., Salas, J. A. (2008). Biosynthesis of elloramycin in Streptomyces olivaceus requires glycosylation by enzymes encoded outside the aglycon cluster. Microbiology 154: 781-788 [Abstract] [Full Text]  
• Zhang, X., Alemany, L. B., Fiedler, H.-P., Goodfellow, M., Parry, R. J. (2008). Biosynthetic Investigations of Lactonamycin and Lactonamycin Z: Cloning of the Biosynthetic Gene Clusters and Discovery of an Unusual Starter Unit. Antimicrob. Agents Chemother. 52: 574-585 [Abstract] [Full Text]  
• Petkovic, H., Cullum, J., Hranueli, D., Hunter, I. S., Peric-Concha, N., Pigac, J., Thamchaipenet, A., Vujaklija, D., Long, P. F. (2006). Genetics of Streptomyces rimosus, the Oxytetracycline Producer. Microbiol. Mol. Biol. Rev. 70: 704-728 [Abstract] [Full Text]  
• Wu, R., Skaar, E. P., Zhang, R., Joachimiak, G., Gornicki, P., Schneewind, O., Joachimiak, A. (2005). Staphylococcus aureus IsdG and IsdI, Heme-degrading Enzymes with Structural Similarity to Monooxygenases. J. Biol. Chem. 280: 2840-2846 [Abstract] [Full Text]  
• Harris, A. K. P., Williamson, N. R., Slater, H., Cox, A., Abbasi, S., Foulds, I., Simonsen, H. T., Leeper, F. J., Salmond, G. P. C. (2004). The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology 150: 3547-3560 [Abstract] [Full Text]  
• Lozano, M. J. F., Remsing, L. L., Quiros, L. M., Brana, A. F., Fernandez, E., Sanchez, C., Mendez, C., Rohr, J., Salas, J. A. (2000). Characterization of Two Polyketide Methyltransferases Involved in the Biosynthesis of the Antitumor Drug Mithramycin by Streptomyces argillaceus. J. Biol. Chem. 275: 3065-3074 [Abstract] [Full Text]  
• Faust, B., Hoffmeister, D., Weitnauer, G., Westrich, L., Haag, S., Schneider, P., Decker, H., Künzel, E., Rohr, J., Bechthold, A. (2000). Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tu2717. Microbiology 146: 147-154 [Abstract] [Full Text]  
• Petkovic, H., Thamchaipenet, A., Zhou, L.-H., Hranueli, D., Raspor, P., Waterman, P. G., Hunter, I. S. (1999). Disruption of an Aromatase/Cyclase from the Oxytetracycline Gene Cluster of Streptomyces rimosus Results in Production of Novel Polyketides with Shorter Chain Lengths. J. Biol. Chem. 274: 32829-32834 [Abstract] [Full Text]  
• Leclerc, G., Wang, S. P., Ely, B. (1998). A New Class of Caulobacter crescentus Flagellar Genes. J. Bacteriol. 180: 5010-5019 [Abstract] [Full Text]  
• Zawada, R. J. X., Khosla, C. (1997). Domain Analysis of the Molecular Recognition Features of Aromatic Polyketide Synthase Subunits. J. Biol. Chem. 272: 16184-16188 [Abstract] [Full Text]  
• Shen, B, Hutchinson, C. (1993). Enzymatic synthesis of a bacterial polyketide from acetyl and malonyl coenzyme A. Science 262: 1535-1540 [Abstract]  
• McDaniel, R, Ebert-Khosla, S, Hopwood, D., Khosla, C (1993). Engineered biosynthesis of novel polyketides. Science 262: 1546-1550 [Abstract]