title: A new mycinosyl rosamicin derivative produced by an engineered Micromonospora rosaria mutant with a cytochrome P450 gene disruption introducing the D-mycinose biosynthetic gene.
abstract: Genetic engineering of post-polyketide synthase-tailoring genes can be used to generate new macrolide analogs through manipulation of the genes involved in their biosynthesis. Rosamicin, a 16-member macrolide antibiotic produced by Micromonospora rosaria IFO13697, contains a formyl group and an epoxide at C-20 and C-12/13 positions which are formed by the cytochrome P450 enzymes RosC and RosD, respectively. The D-mycinose biosynthesis genes in mycinamicin II biosynthesis gene cluster of Micomonospora guriseorubida A11725 were introduced into the rosC and rosD disruption mutants of M. rosaria IFO13697. The resulting engineered strains, M. rosaria TPMA0054 and TPMA0069, produced mycinosyl rosamicin derivatives, IZIV and IZV, respectively. IZIV was identified as a novel mycinosyl rosamicin derivative, 23-O-mycinosyl-20-deoxo-20-dihydrorosamicin.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Iizaka
authors.forename: Noriko
authors.initials: N
authors.lastname: Higashi
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukumoto
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Anzai
authors.forename: Fumio
authors.initials: F
authors.lastname: Kato
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D053898:Biosynthetic Pathways; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005818:Genetic Engineering; D007933:Leucomycins / Q000096:biosynthesis* / Q000737:chemistry; D008847:Micromonospora / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D015394:Molecular Structure; D009154:Mutation; D048630:Polyketide Synthases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007933:Leucomycins; D048630:Polyketide Synthases; D003577:Cytochrome P-450 Enzyme System; C060286:rosaramicin