In vivo characterization of NcsB3 to establish the complete biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore.
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.
Hang
Vu Thi Thu
VT
Department of Pharmaceutical Engineering, Institute of Biomolecule Reconstruction, Sun Moon University, Asansi, Chungnam, Korea.
Oh
Tae Jin
TJ
Yamaguchi
Tokutaro
T
Sohng
Jae Kyung
JK
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
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