Stereochemistry of 10-sulfoxidation catalyzed by a soluble Δ9 desaturase

Abstract

The stereochemistry of castor stearoyl-ACP Delta(9) desaturase-mediated 10-sulfoxidation has been determined. This was accomplished by (19)F NMR analysis of a fluorine-tagged product, 18-fluoro-10-thiastearoyl ACP S-oxide, in combination with a chiral solvating agent, (R)-AMA. Sulfoxidation proceeds with the same stereoselectivity as hydrogen removal from the parent stearoyl substrate. These data validate the use of thia probes to determine the stereochemistry and cryptoregiochemistry of desaturase-mediated oxidations.

Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids

“…[26][27][28][29] However, the sulfur moiety also bestows unique anti-oxidant and desaturase inhibitor properties on these molecules. [30][31][32][33] Mechanistically, two different inhibition pathways have been shown, one involving off-pathway sulfoxidation and one involving carbon-sulfur bond cleavage. 31,32 It is thought that the presence of a thioether or thiol in close proximity to the iron-sulfur cluster of the desaturase leads to inactivation of the enzyme.…”

“…[30][31][32][33] Mechanistically, two different inhibition pathways have been shown, one involving off-pathway sulfoxidation and one involving carbon-sulfur bond cleavage. 31,32 It is thought that the presence of a thioether or thiol in close proximity to the iron-sulfur cluster of the desaturase leads to inactivation of the enzyme. Feeding of thia fatty acids designed to inhibit specific desaturases and observing changes in fatty acid profiles can reveal information about the specificity of uncharacterized enzymes in vivo.…”