title: In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore.
abstract: Neocarzinostatin (NCS) is an enediyne antibiotic produced by Streptomyces carzinostaticus. The NCS chromophore consists of an enediyne core, a sugar moiety, and a naphthoic acid (NA) moiety. The latter plays a key role in binding the NCS chromophore to its apoprotein to protect and stabilize the bioactive NCS chromophore. In this study, we expressed three genes: ncsB (naphthoic acid synthase), ncsB3 (P450 hydroxylase), and ncsB1 (O-methyltransferase), in Streptomyces lividans TK24. The three genes were sufficient to produce 2-hydroxy-7-methoxy-5-methyl-1-naphthoic acid. Production was analyzed and confirmed by LC-MS and nuclear magnetic resonance. Here, we report the functional characterization of ncsB3 and thereby elucidate the complete biosynthetic pathway of NA moiety of the NCS chromophore.
authors.affiliation: Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Asansi, Chungnam, Korea.
authors.forename: Vu Thi Thu
authors.initials: VT
authors.lastname: Hang
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Oh
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D009353:Zinostatin / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002264:Carboxylic Acids; D009281:Naphthalenes; C085312:1-naphthoic acid; C032372:neocarzinostatin chromophore; D009353:Zinostatin; D003577:Cytochrome P-450 Enzyme System