Oxidosqualene cyclase

Oxidosqualene cyclases (OSC) are enzymes involved in cyclization reactions of 2,3-oxidosqualene to form sterols or triterpenes.[1]

The crystal structure of oxidosqualene cyclase shown is colored by secondary structure, with its product, Lanosterol (turquoise) in the enzyme's central active site. The product's characteristic four rings are visible, as is the hydroxyl group on the end of the molecule, which is shown in red.

There are two major groups of sterol-producing OSC enzymes:

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]

  1. ^ a b Thimmappa R, Geisler K, Louveau T, O'Maille P, Osbourn A (29 April 2014). "Triterpene biosynthesis in plants". Annual Review of Plant Biology. 65 (1): 225–257. doi:10.1146/annurev-arplant-050312-120229. PMID 24498976.
  2. ^ Sawai S, Akashi T, Sakurai N, Suzuki H, Shibata D, Ayabe S, Aoki T (May 2006). "Plant lanosterol synthase: divergence of the sterol and triterpene biosynthetic pathways in eukaryotes". Plant & Cell Physiology. 47 (5): 673–677. doi:10.1093/pcp/pcj032. PMID 16531457.
  3. ^ Wendt KU, Poralla K, Schulz GE (September 1997). "Structure and function of a squalene cyclase". Science. 277 (5333): 1811–1815. doi:10.1126/science.277.5333.1811. PMID 9295270. S2CID 30503119.
  4. ^ Lodeiro S, Schulz-Gasch T, Matsuda SP (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. PMID 16218577.