Chemoenzymatic syntheses of prenylated aromatic small molecules using Streptomyces prenyltransferases with relaxed substrate specificities.
NphB is a soluble prenyltransferase from Streptomyces sp. strain CL190 that attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide during the biosynthesis of anti-oxidant naphterpin. Here we report multiple chemoenzymatic syntheses of various prenylated compounds from aromatic substrates including flavonoids using two prenyltransferases NphB and SCO7190, a NphB homolog from Streptomyces coelicolor A3(2), as biocatalysts. NphB catalyzes carbon-carbon-based and carbon-oxygen-based geranylation of a diverse collection of hydroxyl-containing aromatic acceptors. Thus, this simple method using the prenyltransferases can be used to explore novel prenylated aromatic compounds with biological activities. Kinetic studies with NphB reveal that the prenylation reaction follows a sequential ordered mechanism.
Kumano
Takuto
T
Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Richard
Stéphane B
SB
Noel
Joseph P
JP
Nishiyama
Makoto
M
Kuzuyama
Tomohisa
T
D002384:Catalysis; D018360:Crystallography, X-Ray; D004122:Dimethylallyltranstransferase / Q000737:chemistry*; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D008970:Molecular Weight; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013997:Time Factors
D005419:Flavonoids; D018942:Macrolides; D009281:Naphthalenes; C031721:naphthalene; D004122:Dimethylallyltranstransferase