Journal
CHEMBIOCHEM
Volume 14, Issue 15, Pages 1998-2006Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201300370
Keywords
beta-amino acids; biosynthesis; cremimycin; macrolactams; polyketides
Funding
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- Nagase Science and Technology Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [22108003] Funding Source: KAKEN
Ask authors/readers for more resources
Cremimycin is a 19-membered macrolactam glycoside antibiotic based on three distinctive substructures: 1) a -amino fatty acid starter moiety, 2) a bicyclic macrolactam ring, and 3) a cymarose unit. To elucidate the biosynthetic machineries responsible for these three structures, the cremimycin biosynthetic gene cluster was identified. The cmi gene cluster consists of 33 open reading frames encoding eight polyketide synthases, six deoxysugar biosynthetic enzymes, and a characteristic group of five -amino-acid-transfer enzymes. Involvement of the gene cluster in cremimycin production was confirmed by a gene knockout experiment. Further, a feeding experiment demonstrated that 3-aminononanoate is a direct precursor of cremimycin. Two characteristic enzymes of the cremimycin-type biosynthesis were functionally characterized in vitro. The results showed that a putative thioesterase homologue, CmiS1, catalyzes the Michael addition of glycine to the -position of a non-2-enoic acid thioester, followed by hydrolysis of the thioester to give N-carboxymethyl-3-aminononanoate. Subsequently, the resultant amino acid was oxidized by a putative FAD-dependent glycine oxidase homologue, CmiS2, to produce 3-aminononanoate and glyoxylate. This represents a unique amino transfer mechanism for -amino acid biosynthesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available