The Putative Diels−Alderase Macrophomate Synthase is an Efficient Aldolase
- 31 May 2008
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 130 (25), 7798-7799
- https://doi.org/10.1021/ja8017994
Abstract
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 γ-hydroxy-α-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.Keywords
This publication has 17 references indexed in Scilit:
- Trapping and Structural Elucidation of an Intermediate in the Macrophomate Synthase Reaction PathwayJournal of the American Chemical Society, 2007
- Macrophomate Synthase: QM/MM Simulations Address the Diels−Alder versus Michael−Aldol Reaction MechanismJournal of the American Chemical Society, 2005
- Chemistry and Biology of Biosynthetic Diels–Alder ReactionsAngewandte Chemie-International Edition, 2003
- Insight into a natural Diels–Alder reaction from the structure of macrophomate synthaseNature, 2003
- Detailed Reaction Mechanism of Macrophomate SynthaseJournal of Biological Chemistry, 2000
- Crystal structures of the metal-dependent 2-dehydro-3-deoxy-galactarate aldolase suggest a novel reaction mechanismThe EMBO Journal, 2000
- Evolution of Enzymatic Activities in the Enolase Superfamily: Characterization of the (D)-Glucarate/Galactarate Catabolic Pathway in Escherichia coliBiochemistry, 1998
- Stereospecific Preparation of the N-Terminal Amino Acid Moiety of Nikkomycins KX and KZ via a Multiple Enzyme SynthesisThe Journal of Organic Chemistry, 1997
- Biosynthesis of macrophomic acid: plausible involvement of intermolecular Diels–Alder reactionChemical Communications, 1997
- (Cyanomethylene)phosphoranes as Novel Carbonyl 1,1-Dipole Synthons: An Efficient Synthesis of .alpha.-Keto Acids, Esters, and AmidesThe Journal of Organic Chemistry, 1994