Recombinant Saccharomyces cerevisiae Lanosterol 14-alpha demethylase (ERG11), partial

Function

Sterol 14alpha-demethylase that plays a critical role in the third module of ergosterol biosynthesis pathway, being ergosterol the major sterol component in fungal membranes that participates in a variety of functions (PubMed:105731, PubMed:369554). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (PubMed:32679672). Starting from lanosterol (lanosta-8,24-dien-3beta-ol), it catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of the sterol in the form of formate, and converts the sterol to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, which is critical for ergosterol biosynthesis (PubMed:105731, PubMed:3543000, PubMed:369554). Can demethylate substrates not intrinsic to yeast, such as eburicol (24-methylene-24,25-dihydrolanosterol) at a similar rate to lanosterol, and at a lower rate the 24,25-dihydrolanosterol (DHL) to 4,4-dimethyl-8,14-cholestadien-3beta-ol (PubMed:1872829, PubMed:3543000)

Subcellular Location

Endoplasmic reticulum membrane (Single-pass membrane protein)

Subunit

Interacts with ERG28

Pathway

Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6

• Kalb V.F. et al. Primary structure of the P450 lanosterol demethylase gene from Saccharomyces cerevisiae. — DNA (1987)
• Ishida N. et al. A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary structures deduced from cloned DNAS. — Biochem. Biophys. Res. Commun. (1988)
• Johnston M. et al. Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. — Science (1994)
• Engel S.R. et al. The reference genome sequence of Saccharomyces cerevisiae: Then and now. — G3 (Bethesda) (2014)
• Kalb V.F. et al. Isolation of a cytochrome P-450 structural gene from Saccharomyces cerevisiae. — Gene (1986)
• Ohba M. et al. Involvement of cytochrome P-450 and a cyanide-sensitive enzyme in different steps of lanosterol demethylation by yeast microsomes. — Biochem. Biophys. Res. Commun. (1978)
• Aoyama Y. et al. The 14alpha-demethylation of lanosterol by a reconstituted cytochrome P-450 system from yeast microsomes. — Biochem. Biophys. Res. Commun. (1978)
• Aoyama Y. et al. Metabolism of 32-hydroxy-24,25-dihydrolanosterol by purified cytochrome P-45014DM from yeast. Evidence for contribution of the cytochrome to whole process of lanosterol 14 alpha-demethylation. — J. Biol. Chem. (1987)