Involvement of glutamate mutase in the biosynthesis of the unique starter unit of the macrolactam polyketide antibiotic vicenistatin.
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.
Ogasawara
Yasushi
Y
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo, 152-8551, Japan.
Kakinuma
Katsumi
K
Eguchi
Tadashi
T
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
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D007769:Lactams; D018942:Macrolides; C082785:vicenistatin; D048630:Polyketide Synthases; D019751:Intramolecular Transferases; C021570:methylaspartate mutase