CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis.

摘要: During the biosynthesis of streptomycete aminocoumarin antibiotics novobiocin and dimeric coumermycin A1, bicyclic coumarin scaffold is C-methylated adjacent to phenolic oxygen. The SAM-dependent C-methyltransferases NovO CouO have been heterologously expressed purified from Escherichia coli shown act after ring has constructed by prior action Nov/CouHIJK. Neither C-methyltransferase works on tyrosyl-derived S-pantetheinyl intermediates tethered NovH or subsequently released free aminocoumarin. NovL ligates prenylhydroxybenzoate yield novobiocic acid, which substrate for before it O-glycosylated NovM. In assembly, corresponding ligase CouL makes bis-amide tandem ligation two aminocoumarins a dicarboxypyrrole. both mono- bis-amides di-C-methylation hydroxyl glycosylated CouM. Thus, speci...