Metabolism of ganoderic acids by a Ganoderma lucidum cytochrome P450 and the 3-keto sterol reductase ERG27 from yeast.

Abstract Ganoderic acids, a group of oxygenated lanostane-type triterpenoids, are the major bioactive compounds produced by the well-known medicinal macro fungus Ganoderma lucidum. More than 150 ganoderic acids have been identified, and the genome of G. lucidum has been sequenced recently. However, the biosynthetic pathways of ganoderic acids have not yet been elucidated. Here, we report the functional characterization of a cytochrome P450 gene CYP512U6 from G. lucidum, which is involved in the ganoderic acid biosynthesis. CYP512U6 hydroxylates the ganoderic acids DM and TR at the C-23 position to produce hainanic acid A and ganoderic acid Jc, respectively. In addition, CYP512U6 can also hydroxylate a modified ganoderic acid DM in which the C-3 ketone has been reduced to hydroxyl by the sterol reductase ERG27 from Saccharomyces cerevisiae. An NADPH-dependent cytochrome P450 reductase from G. lucidum was also isolated and characterized. These results will help elucidate the biosynthetic pathways of ganoderic acids. Graphical abstract Image 1 Highlights • A cytochrome P450, CYP512U6, hydroxylating C-23-H of ganoderic acid DM and TR was characterized. • The sterol reductase ERG27 from yeast can reduce the C-3 ketone of ganoderic acid DM to hydroxyl. • GLCPR , a cytochrome P450 reductase gene from Ganoderma lucidum , was isolated and characterized. • An undescribed metabolite is identified as a C-23 hydroxyl derivative of 7-oxo-gaonoderic acid Z. [ABSTRACT FROM AUTHOR]