Steric Bulk at Cycloartenol Synthase Position 481 Influences Cyclization and Deprotonation

• Published in: Organic letters Vol. 2; no. 15; pp. 2261 - 2263
• Main Authors: Matsuda, Seiichi P. T, Darr, Lisa B, Hart, Elizabeth A, Herrera, Jennifer B. R, McCann, Kelly E, Meyer, Michelle M, Pang, Jihai, Schepmann, Hala G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27-07-2000
• Subjects: Amino Acid Substitution; Arabidopsis - enzymology; Arabidopsis - genetics; Cyclization; Gas Chromatography-Mass Spectrometry; Intramolecular Transferases - chemistry; Intramolecular Transferases - genetics; Intramolecular Transferases - metabolism; Lanosterol - analogs & derivatives; Lanosterol - biosynthesis; Lanosterol - metabolism; Magnetic Resonance Spectroscopy; Mutation; Phytosterols - biosynthesis; Phytosterols - metabolism; Protons; Structure-Activity Relationship; Triterpenes
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol006018w

Cycloartenol synthase converts oxidosqualene to the pentacyclic sterol precursor cycloartenol. An Arabidopsis thaliana cycloartenol synthase Ile481Val mutant was previously shown to produce lanosterol and parkeol in addition to its native product cycloartenol. Experiments are described here to construct Phe, Leu, Ala, and Gly mutants at position 481 and to determine their cyclization product profiles. The Phe mutant was inactive, and the Leu mutant produced cycloartenol and parkeol. The Ala and Gly mutants formed lanosterol, cycloartenol, parkeol, achilleol A, and camelliol C. Monocycles comprise most of the Gly mutant product, showing that an alternate cyclization route can be made the major pathway by a single nonpolar mutation.