Oxidosqualene cyclase
Oxidosqualene cyclases (OSC) are enzymes involved in cyclization reactions of 2,3-oxidosqualene to form sterols or triterpenes.[1] There are two major groups of sterol-producing OSC enzymes:
- Cycloartenol synthase (CAS), found in all plants, which produces primarily cycloartenol
- Lanosterol synthase (LAS), found in all animals and fungi, and occasionally in plants, which produces primarily lanosterol
Sterols and triterpenes are extremely diverse classes of natural products, particularly in plants, which often contain numerous OSC enzymes with different substrate and product specificities;[1] common examples include lupeol synthase and beta-amyrin synthase.[2] OSC enzymes' catalytic mechanism is similar to the prokaryotic squalene-hopene cyclase.[3]
Directed evolution and protein design have been used to identify small numbers of point mutations that alter the product specificities of OSC enzymes, most notably in altering a cycloartenol synthase to produce predominantly lanosterol.[4]
References
- 1 2 Thimmappa, Ramesha; Geisler, Katrin; Louveau, Thomas; O'Maille, Paul; Osbourn, Anne (29 April 2014). "Triterpene Biosynthesis in Plants". Annual Review of Plant Biology 65 (1): 225–257. doi:10.1146/annurev-arplant-050312-120229.
- ↑ Sawai, S. (15 March 2006). "Plant Lanosterol Synthase: Divergence of the Sterol and Triterpene Biosynthetic Pathways in Eukaryotes". Plant and Cell Physiology 47 (5): 673–677. doi:10.1093/pcp/pcj032.
- ↑ Wendt, KU; Poralla, K; Schulz, GE (19 September 1997). "Structure and function of a squalene cyclase.". Science (New York, N.Y.) 277 (5333): 1811–5. PMID 9295270.
- ↑ Lodeiro, Silvia; Schulz-Gasch, Tanja; Matsuda, Seiichi P. T. (October 2005). "Enzyme Redesign: Two Mutations Cooperate to Convert Cycloartenol Synthase into an Accurate Lanosterol Synthase". Journal of the American Chemical Society 127 (41): 14132–14133. doi:10.1021/ja053791j.