MenD as a versatile catalyst for asymmetric synthesis

作者：Kurutsch Anja; Richter Michael; Brecht Volker; Sprenger Georg A; Mueller Michael

来源：Journal of Molecular Catalysis B: Enzymatic , 2009, 61(1-2): 56-66.

DOI：10.1016/j.molcatb.2009.03.011

• Biocatalysis
• Shikimate pathway
• SHCHC-synthase
• Enantioselective
• Carboligation

The thiamine diphosphate (ThDP)-dependent enzyme 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase (MenD) from Escherichia coli K12, formerly known as SHCHC-synthase, catalyses the decarboxylation of alpha-ketoglutarate and the subsequent addition of the resulting succinyl-THDP to isochorismate. Here, the enzyme is tested for unphysiologial C-C bond-forming reactions.
Condensation of alpha-ketoglutarate after decarboxylation to a broad range of aldehydes gave alpha-hydroxyketones with isolated yields from 26 to 87% and 94 to 98% ee for addition to aromatic aldehydes. MenD accepts a wide range of aldehydes as acceptor substrates to produce chiral alpha-hydroxyketones with conserved regioselectivity where the activated succinylsemialdehyde serves selectively as the donor. Regioselectivity is inverted only for condensation of alpha-ketoglutarate with pyruvate (activated acetaldehyde) as donor. Besides alpha-ketoglutarate, pyruvate and oxalacetate are accepted as donors in combination with benzaldehyde and 2-fluorobenzaldehyde as acceptors, however with decreased activity of C-C bond formation.
The physiological 1,4-addition of alpha-ketoglutarate to isochorismate was investigated for acceptor substrate variability. (2S,3S)-2,3-Dihydroxy-2,3-dihydrobenzoate (2,3-CHD), which lacks the pyruvyl found in isochorismate, is converted to (5S,6S)-2-succinyl-5,6-dihydroxycyclohex-2-enecarboxylate. In contrast to the addition to carbonyls, the active site of MenD does appear to impose specific constraints on the acceptor substrate for 1.4-addition with alpha,beta-unsaturated carboxylic acids.

• 出版日期2009-11