Identification and characterization of gerPI and gerPII involved in epoxidation and hydroxylation of dihydrochalcolactone in Streptomyces species KCTC 0041BP.
The macrolide antibiotics are biosynthesized by initial assembly of a macrolactone ring, followed by a series of post-polyketide (PKS) modifications. In general, the additional hydroxyl or epoxy groups are installed by cytochrome P450 enzymes, improving the bioactivity profile through structural diversification of natural products. The biosynthetic gene cluster for the 16-membered macrolide antibiotic dihydrochalcomycin (DHC) has been cloned from Streptomyces sp. KCTC 0041BP. Three cytochrome P450 genes are found in the DHC biosynthetic gene (ger) cluster. Two P450 enzymes were characterized from this cluster. Disruption of gerPI accumulated predominantly 12,13-de-epoxydihydrochalcomycin while disruption of gerPII accumulated 8-dehydroxy-12,13-de-epoxydihydrochalcomycin; DHC production was abolished in both cases. The results suggest that GerPII P450 catalyzes hydroxylation at the C(8) position followed by an epoxidation reaction catalyzed by GerPI P450 at the C(12)-C(13) position.
Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, SunMoon University, # 100 Kalsan-ri, Asansi, Chungnam 336-708, Korea.
Sailesh
S
Malla
Ta Thi Thu
TT
Thuy
Tae Jin
TJ
Oh
Jae Kyung
JK
Sohng
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006027:Glycosides / Q000096:biosynthesis* / Q000737:chemistry*; D006900:Hydroxylation; D018942:Macrolides / Q000737:chemistry*; D008969:Molecular Sequence Data; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D006027:Glycosides; D018942:Macrolides; C549885:dihydrochalcomycin; D003577:Cytochrome P-450 Enzyme System