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.

中文翻译：

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灵芝细胞色素 P450 和酵母 3-酮甾醇还原酶 ERG27 对灵芝酸的代谢

灵芝酸是一组含氧羊毛脂烷型三萜类化合物，是著名的药用大型真菌灵芝产生的主要生物活性化合物。已鉴定出 150 多种灵芝酸，最近对灵芝的基因组进行了测序。然而，灵芝酸的生物合成途径尚未阐明。在这里，我们报告了灵芝细胞色素 P450 基因 CYP512U6 的功能表征，该基因参与灵芝酸生物合成。CYP512U6 在 C-23 位将灵芝酸 DM 和 TR 羟基化，分别产生海南酸 A 和灵芝酸 Jc。此外，CYP512U6 还可以羟基化修饰的灵芝酸 DM，其中 C-3 酮已被来自酿酒酵母的甾醇还原酶 ERG27 还原为羟基。还分离并表征了来自灵芝的 NADPH 依赖性细胞色素 P450 还原酶。这些结果将有助于阐明灵芝酸的生物合成途径。