The putative Diels-Alderase macrophomate synthase is an efficient aldolase.
We find that the putative Diels-Alderase macrophomate synthase (MPS) catalyzes the addition of pyruvate enolate, generated by decarboxylation of oxaloacetate, to a variety of aldehydes. Alkyl, aryl, and heteroaryl aldehydes are accepted as substrates, providing gamma-hydroxy-alpha-ketoacids in 35-95% yield with modest levels of stereochemical control. These aldol products, which are difficult to synthesize by other methods, are formed with efficiency comparable to that of macrophomate. Our results thus provide evidence that a two-step Michael-aldol pathway is a plausible alternative to the postulated [4 + 2] cycloaddition in the MPS-catalyzed addition of pyruvate enolate to 2-pyrones. They are also relevant to understanding the divergent evolution of type II pyruvate aldolases.
Serafimov
Jörg M
JM
Laboratory of Organic Chemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
Gillingham
Dennis
D
Kuster
Simon
S
Hilvert
Donald
D
D002384:Catalysis; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry*; D009097:Multienzyme Complexes / Q000737:chemistry*; D011487:Protein Conformation
D009097:Multienzyme Complexes; C408144:macrophomate synthase; D005634:Fructose-Bisphosphate Aldolase