Project Details
Projekt
Anaerobic bacterial metabolism of cholesterol
Applicant
Professor Dr. Matthias Boll
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
from 2008 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 72005129
Cholesterol is one of the most abundant steroids in the nature. The anoxic metabolism of this ubiquitous triterpene is challenging because of its complex chemical structure, low solubility in water, low number of active functional groups, the presence of four alicyclic rings and two quaternary carbon atoms. Consequently, the aerobic metabolism of cholesterol depends on oxygenase catalyzed reactions requiring molecular oxygen as co-substrate. Sterolibacterium denitrificans was shown to metabolize cholesterol completely without oxygen via the oxidation of ring A, followed by an oxygen independent hydroxylation of the terminal C-25 of the side chain. The enzymes catalyzing these initial reactions were purified and charcterized in some detail. The most intriguing enzyme is the C-25 side chain hydroxylase belonging to the Mo-cofactor containing family of DMSO reductases. The structure and function of this unique enzyme will be investigated in detail. The genome sequence of S. denitrificans revealed a number of genes that code for putative similar Mo-containing hydroxylases, and that are predicted to catalyze so far non-characterized oxygen-independent hydroxylation reaction in the anaerobic catabolism of cholesterol. The role of such enzymes in anoxic cholesterol degradation steps will be studied by proteomic and metabolomic approaches.
DFG Programme
Priority Programmes
