Biosynthesis of 2'-O-methylmyxalamide D in the myxobacterium Cystobacter fuscus: a polyketide synthase-nonribosomal peptide synthetase system for the myxalamide D skeleton and a methyltransferase for the final O-methylation.
The biosynthetic gene cluster for the polyene antifungal antibiotic, 2'-O-methylmyxalamide D, was cloned from myxobacterium Cystobacter fuscus AJ-13278. A sequence analysis of the 12.8-kb region in the gene cluster revealed the presence of two type I polyketide synthase genes, mmxB and mmxC. The involvement of these two genes in the biosynthesis of 2'-O-methylmyxalamide D was confirmed by a gene disruption experiments. In addition, an S-adenosylmethionine-dependent methyltransferase gene (mmxM) was found downstream of the gene cluster and demonstrated, by a gene disruption analysis, to be responsible for converting the known unmethylated precursor, myxalamide D, into 2'-O-methylmyxalamide D.
Feng
Zhiyang
Z
Graduate School of Bioagricultural Sciences, Nagoya University, Japan.
Qi
Jianhua
J
Tsuge
Takashi
T
Oba
Yuichi
Y
Sakagami
Youji
Y
Ojika
Makoto
M
D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D005810:Multigene Family / Q000235:genetics; D009231:Myxococcales / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D010453:Peptide Synthases / Q000378:metabolism*; D011090:Polyenes / Q000737:chemistry / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism*; D012270:Ribosomes / Q000201:enzymology
C511236:2'-O-methylmyxalamide D; D004269:DNA, Bacterial; D011090:Polyenes; D048630:Polyketide Synthases; C039625:myxalamid D; D008780:Methyltransferases; D010453:Peptide Synthases