The role of erythromycin C-12 hydroxylase, EryK, as a substitute for PikC hydroxylase in pikromycin biosynthesis.
The substrate flexibility of the erythromycin C-12 hydroxylase from Saccharopolyspora erythraea, EryK, was investigated to test its potential for the generation of novel polyketide structures. We have shown that EryK can accept the substrates of PikC from Streptomyces venezuelae which is responsible for the hydroxylation of YC-17 and narbomycin. In a S. venezuelae pikC deletion mutant, EryK could catalyze the hydroxylation of YC-17 and narbomycin to generate methymycin/neomethymycin and pikromycin, respectively. Molecular modeling of the enzyme-substrate complex suggested the possible interaction of EryK with alternative substrates. The results indicate that EryK is flexible toward some alternative polyketides and can be useful for structural diversification of macrolides by post-polyketide synthase hydroxylation.
Lee
Sang Kil
SK
School of Chemical Engineering, College of Engineering, Seoul National University, San 56-1, Sinlim-dong, Gwanak-gu 151-742, Republic of Korea.
Basnet
Devi B
DB
Choi
Cha Yong
CY
Sohng
Jae Kyung
JK
Ahn
Jong Seog
JS
Yoon
Yeo Joon
YJ
D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000502:physiology*; D006900:Hydroxylation; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000502:physiology*; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D016930:Saccharopolyspora / Q000201:enzymology; D013045:Species Specificity; D013302:Streptomyces / Q000201:enzymology; D013379:Substrate Specificity
D001426:Bacterial Proteins; D018942:Macrolides; C116391:YC-17 macrolide; C010488:narbomycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C078882:EryK protein, Saccharopolyspora erythraea; C003145:picromycin