Emergent mechanistic diversity of enzyme-catalysed beta-diketone cleavage.
The enzymatic cleavage of C-C bonds in beta-diketones is, comparatively, a little studied biochemical process, but one that has important relevance to human metabolism, bioremediation and preparative biocatalysis. In recent studies, four types of enzymes have come to light that cleave C-C bonds in the beta-diketone functionality using different chemical mechanisms. OPH [oxidized poly(vinyl alcohol) hydrolase from Pseudomonas sp. strain VM15C], which cleaves nonane-4,6-dione to butyrate and pentan-2-one is a serine-triad hydrolase. Dke1 (diketone-cleaving enzyme from Acinetobacter johnsonii) is a dioxygenase, cleaving acetylacetone to methylglyoxal and acetate. Fumarylacetoacetate hydrolase cleaves fumarylacetoacetate to fumarate and acetoacetate using a water molecule, activated by a catalytic His/Asp dyad, aided by a calcium ion that both chelates the enol acid form of the substrate and indirectly positions the water for nucleophilic attack at a carbonyl group. 6-oxocamphor hydrolase cleaves nonenolizable cyclic beta-diketones and is a homologue of the crotonase superfamily, employing a catalytic His/Asp dyad to activate a water molecule for nucleophilic attack at a carbonyl group on one prochiral face of the diketone substrate, effecting desymmetrizations of symmetrical substrates.
Grogan
Gideon
G
York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York, YO10 5YW, UK. grogan@ysbl.york.ac.uk
D000818:Animals; D001419:Bacteria / Q000201:enzymology; D049308:Dioxygenases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism*; D007659:Ketones / Q000737:chemistry*; D011487:Protein Conformation
D007659:Ketones; D049308:Dioxygenases; D006867:Hydrolases