Reaction: abieta-8,11,13-triene + [reduced NADPH—hemoprotein reductase] + O2 = ferruginol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of abietane diterpenoids biosynthesis, click here
Glossary: ferruginol = abieta-8,11,13-trien-12-ol
Other name(s): miltiradiene oxidase (incorrect); CYP76AH1; miltiradiene,NADPH:oxygen oxidoreductase (ferruginol forming) (incorrect)
Systematic name: abieta-8,11,13-triene,[NADPH–hemoprotein reductase]:oxygen 12-oxidoreductase (ferruginol-forming)
Comments: A cytochrome P-450 (heme thiolate) enzyme found in some members of the Lamiaceae (mint family). The enzyme from Rosmarinus officinalis (rosemary) is involved in biosynthesis of carnosic acid, while the enzyme from the Chinese medicinal herb Salvia miltiorrhiza is involved in the biosynthesis of the tanshinones, abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components found in the plant.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Guo, J., Zhou, Y.J., Hillwig, M.L., Shen, Y., Yang, L., Wang, Y., Zhang, X., Liu, W., Peters, R.J., Chen, X., Zhao, Z.K. and Huang, L. CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts. Proc. Natl. Acad. Sci. USA 110 (2013) 12108-12113. [PMID: 23812755]
2. Zi, J. and Peters, R.J. Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the Lamiaceae. Org. Biomol. Chem. 11 (2013) 7650-7652. [PMID: 24108414]
3. Bozic, D., Papaefthimiou, D., Bruckner, K., de Vos, R.C., Tsoleridis, C.A., Katsarou, D., Papanikolaou, A., Pateraki, I., Chatzopoulou, F.M., Dimitriadou, E., Kostas, S., Manzano, D., Scheler, U., Ferrer, A., Tissier, A., Makris, A.M., Kampranis, S.C. and Kanellis, A.K. Towards elucidating carnosic acid biosynthesis in Lamiaceae: functional characterization of the three first steps of the pathway in Salvia fruticosa and Rosmarinus officinalis. PLoS One 10 (2015) e0124106. [PMID: 26020634]