Structure-function analysis for the hydroxylation of Delta 4 C21-steroids by the myxobacterial CYP260B1

TitleStructure-function analysis for the hydroxylation of Delta 4 C21-steroids by the myxobacterial CYP260B1
Publication TypeJournal Article
Year of Publication2016
AuthorsSalamanca-Pinzon S.G, Khatri Y., Carius Y., Keller L., Muller R, Lancaster C.RD, Bernhardt R.
JournalFebs Letters
Volume590
Pagination1838-1851
Date Published2016/06
Type of ArticleArticle
ISBN Number0014-5793
Accession NumberWOS:000379153500017
Keywordsbiosynthesis; ce56; CYP260B1; cytochromes p450; gene-cluster; identification; liver-microsomes; pigment; products; site-directed mutagenesis; Sorangium cellulosum; sorangium-cellulosum; steroid
Abstract

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.

DOI10.1002/1873-3468.12217
Short TitleFEBS Lett.
Student Publication: 
No
sharknado