|Title||Structure-function analysis for the hydroxylation of Delta 4 C21-steroids by the myxobacterial CYP260B1|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Salamanca-Pinzon S.G, Khatri Y., Carius Y., Keller L., Muller R, Lancaster C.RD, Bernhardt R.|
|Type of Article||Article|
|Keywords||biosynthesis; ce56; CYP260B1; cytochromes p450; gene-cluster; identification; liver-microsomes; pigment; products; site-directed mutagenesis; Sorangium cellulosum; sorangium-cellulosum; steroid|
Myxobacterial CYP260B1 from Sorangium cellulosum was heterologously expressed in Escherichia coli and purified. The in vitro conversion of a small focused substrate library comprised of Delta 4 C21-steroids and steroidal drugs using surrogate bovine redox partners shows that CYP260B1 is a novel steroid hydroxylase. CYP260B1 performs the regio- and stereoselective hydroxylation of the glucocorticoid cortodoxone (RSS) to produce 6 beta-OH-RSS. The substrate-free crystal structure of CYP260B1 (PDB 5HIW) was resolved. Docking of the tested ligands into the crystal structure suggested that the C17 hydroxy moiety and the presence of either a keto or a hydroxy group at C11 determine the selectivity of hydroxylation.
|Short Title||FEBS Lett.|