Identification of tailoring genes involved in the modification of the polyketide backbone of rifamycin B by Amycolatopsis mediterranei S699.
Rifamycin B biosynthesis by Amycolatopsis mediterranei S699 involves a number of unusual modification reactions in the formation of the unique polyketide backbone and decoration of the molecule. A number of genes believed to be involved in the tailoring of rifamycin B were investigated and the results confirmed that the formation of the naphthalene ring moiety of rifamycin takes place during the polyketide chain extension and is catalysed by Rif-Orf19, a 3-(3-hydroxyphenyl)propionate hydroxylase-like protein. The cytochrome P450-dependent monooxygenase encoded by rif-orf5 is required for the conversion of the Delta12, 29 olefinic bond in the polyketide backbone of rifamycin W into the ketal moiety of rifamycin B. Furthermore, Rif-Orf3 may be involved in the regulation of rifamycin B production, as its knock-out mutant produced about 40 % more rifamycin B than the wild-type. The work also revealed that many of the genes located in the cluster are not involved in rifamycin biosynthesis, but might be evolutionary remnants carried over from an ancestral lineage.
Xu
Jun
J
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Wan
Eva
E
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331-3507, USA.|Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Kim
Chang-Joon
CJ
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Floss
Heinz G
HG
Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
Mahmud
Taifo
T
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331-3507, USA.|Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
D039903:Actinobacteria / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000595:Amino Acid Sequence; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D018942:Macrolides / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D016366:Open Reading Frames; D012294:Rifamycins / Q000096:biosynthesis* / Q000737:chemistry
D018942:Macrolides; D009097:Multienzyme Complexes; D012294:Rifamycins