Abstract
The macrolactam antibiotic vicenistatin, produced in Streptomyces halstedii HC34, is biosynthesized by the polyketide pathway, using a unique 3-methylaspartate-derived molecule as starter unit. The vinI gene in the vicenistatin biosynthetic gene cluster encoding glutamate mutase, which rearranges glutamate to 3-methylaspartate, was disrupted. The vinI disruption completely abolished the production of vicenistatin, while the disruptant recovered the production of vicenistatin when 3-methylaspartate was added to the culture. These results indicate that vinI is essential for the 3-methylaspartate formation in the vicenistatin biosynthesis. Furthermore, the mutant accumulated new vicenistatin derivatives (desmethylvicenistatins), which lacked a methyl group in the starter unit. The desmethylvicenistatins were shown by feeding experiments to be derived from aspartate instead of 3-methylaspartate as the starter unit. These results indicate that the vicenistatin polyketide synthase can accept alternative starter units toward the production of novel polyketides.
Similar content being viewed by others
Article PDF
References
Shindo K, Kamishohara M, Odagawa A, Matsuoka M, Kawai H . Vicenistatin, a novel 20-membered macrocyclic lactam antitumor antibiotic. J Antibiot 46: 1076–1081 ( 1993)
Otsuka M, Eguchi T, Shindo K, Kakinuma K . Non-fatty acyl polyketide starter in the biosynthesis of vicenistatin, an antitumor macrolactam antibiotic. Tetrahedron Lett 39: 3185–3188 ( 1998)
Otsuka M, Fujita M, Matsushima Y, Eguchi T, Shindo K, Kakinuma K . Biosynthetic pathway of macrolactam polyketide glycoside antitumor antibiotic vicenistatins. Tetrahedron 56: 8281–8286 ( 2000)
Nishida H, Eguchi T, Kakinuma K . Amino acid starter unit in the biosynthesis of macrolactam polyketide antitumor antibiotic vicenistatin. Tetrahedron 57: 8237–8242 ( 2001)
Hoffmann B, Konrat R, Bothe H, Buckel W, Krautler B . Structure and dynamics of the B12-binding subunit of glutamate mutase from Clostridium cochlearium. Eur J Biochem 263: 178–188 ( 1999)
Ogasawara Y, Katayama K, Minami A, Otsuka M, Eguchi T, Kakinuma K . Cloning, sequencing, and functional analysis of the biosynthetic gene cluster of macrolactam antibiotic vicenistatin in Streptomyces halstedii. Chem Biol 11: 79–86 ( 2004)
Vara J, Lewandowska-Skarbek M, Wang YG, Donadio S, Hutchinson CR . Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in Saccharopolyspora erythraea (Streptomyces erythreus). J Bacteriol 171: 5872–5881 ( 1989)
Blondelet-Rouault MH, Weiser J, Lebrihi A, Branny P, Pernodet JL . Antibiotic resistance gene cassettes derived from the omega interposon for use in E. coli and Streptomyces. Gene 190: 315–317 ( 1997)
Tamiya N, Oshima T . Synthesis of deuterium derivatives of L-aspartic acid. J Biochem 51: 78–88 ( 1962)
Hanai K, Kuwae A . Preparation of β-alanine-3,3-D2 and -2,2,3,3-D4 . J Labeled Compd Radiopharm 25: 217–224 ( 1987)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ogasawara, Y., Kakinuma, K. & Eguchi, T. Involvement of Glutamate Mutase in the Biosynthesis of the Unique Starter Unit of the Macrolactam Polyketide Antibiotic Vicenistatin. J Antibiot 58, 468–472 (2005). https://doi.org/10.1038/ja.2005.62
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ja.2005.62
Keywords
This article is cited by
-
Semi-synthesis and structure-activity relationship study yield antibacterial vicenistatin derivatives with low cytotoxicity
The Journal of Antibiotics (2024)
-
Identification of a biosynthetic gene cluster for the polyene macrolactam sceliphrolactam in a Streptomyces strain isolated from mangrove sediment
Scientific Reports (2018)
-
Identification of the incednine biosynthetic gene cluster: characterization of novel β-glutamate-β-decarboxylase IdnL3
The Journal of Antibiotics (2013)
-
The Complete Biosynthetic Gene Cluster of the 28-Membered Polyketide Macrolactones, Halstoctacosanolides, from Streptomyces halstedii HC34
The Journal of Antibiotics (2006)