title: Production of a hybrid 16-membered macrolide antibiotic by genetic engineering of Micromonospora sp. TPMA0041.
abstract: Some polyketide-derived bioactive compounds contain sugars attached to the aglycone core, and these sugars often enhance or impart specific biological activity to the molecule. Mycinamicin II, a 16-member macrolide antibiotic produced by Micromonospora griseorubida A11725, contains a branched lactone and two different deoxyhexose sugars, D-desosamine and D-mycinose, at the C-5 and C-21 positions, respectively. We previously engineered an expression plasmid pSETmycinose containing the D-mycinose biosynthesis genes from M. griseorubida A11725. This plasmid was introduced into Micromonospora sp. FERM BP-1076 cells, which produce the 16-membered macrolide antibiotic izenamicin. The resulting engineered strain TPMA0041 produced 23-O-mycinosyl-20-deoxy-izenamicin B(1) and 22-O-mycinosyl-izenamicin B(2). 23-O-mycinosyl-20-deoxy-izenamicin B(1) has been produced by the engineered strain M. rosaria TPMA0001 containing pSETmycinose as 23-O-mycinosyl-20-deoxo-20-dihydro-12,13-deepoxyrosamicin (=IZI) in our recent study, and 22-O-mycinosyl-izenamicin B(2) has previously been synthesized as a macrolide antibiotic TMC-016 with strong antibacterial activity. The production of 22-O-mycinosyl-izenamicin B(2) (=TMC-016) was increased when propionate, a precursor of methylmalonyl-CoA, was added to the culture broth.
authors: Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors: Ayami
authors: A
authors: Sakai
authors: Aki
authors: A
authors: Mitsumori
authors: Mika
authors: M
authors: Furukawa
authors: Kenji
authors: K
authors: Kinoshita
authors: Yojiro
authors: Y
authors: Anzai
authors: Fumio
authors: F
authors: Kato
mesh_terms: D000606:Amino Sugars / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D053898:Biosynthetic Pathways / Q000235:genetics; D005818:Genetic Engineering; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008847:Micromonospora / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics; D015645:Tylosin / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D018942:Macrolides; C026686:mycinamicins; C110125:desosamine; C060112:TMC 016; D015645:Tylosin