Fig. 1: The design principle of recursive carboligation cycle for β,γ-diol synthesis.
From: Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism
a Proposed recursive carboligation mediated by bifunctional acetohydroxyacid synthase (AHAS) for the synthesis of β,γ-diols. Acetohydroxyacid synthase, AHAS. b The L-valine pathway as an example to demonstrate the recursive carboligation mediated by AHAS for 4-M-PDO synthesis. AHAS catalyzes pyruvate to bind with thiamine diphosphate (ThDP), to form lactyl-ThDP (process 1). AHAS then catalyzes the decarboxylation of pyruvate in lactyl-ThDP to form hydroxyethyl-ThDP anion/enamine (HEThDP) (process 2). Subsequently, the HEThDP intermediate binds to aldehydes derived from the decarboxylation of 2-ketoacids, to form α-hydroxyketone-ThDP (process 6). α-Hydroxyketones are released, and AHAS, ThDP returns to the cycle (process 7). Diols such as 4-methylpentane-2,3-diol (4-M-PDO) are produced by further reduction of α-hydroxyketones by AKR and sADH (process 8). Processes (1 ~ 5) represent the steps for 2-ketoisovalerate synthesis and its decarboxylation to isobutyraldehyde. c Potential diols from the branched-chain amino acid (BCAA) metabolism. Abbreviations: AHAS acetohydroxyacid synthase, KDC 2-ketoacid decarboxylase, AKR aldehyde-keto reductase, sADH secondary alcohol dehydrogenase.
