title: Involvement of glutamate mutase in the biosynthesis of the unique starter unit of the macrolactam polyketide antibiotic vicenistatin.
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.
authors.affiliation: Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo, 152-8551, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ogasawara
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kakinuma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Eguchi
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D019751:Intramolecular Transferases / Q000502:physiology*; D007769:Lactams / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry; D015394:Molecular Structure; D048630:Polyketide Synthases / Q000502:physiology*; D013302:Streptomyces / Q000201:enzymology* / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007769:Lactams; D018942:Macrolides; C082785:vicenistatin; D048630:Polyketide Synthases; D019751:Intramolecular Transferases; C021570:methylaspartate mutase