acetaldehyde

Acetaldehyde is a metabolic intermediate of alcoholic fermentation pathways. In these pathways, pyruvate is converted into acetaldehyde via a decarboxylation reaction catalyzed by the enzyme pyruvate decarboxylase [49]. Acetaldehyde is subsequently reduced to ethanol by fermentative isozymes of alcohol dehydrogenase, such as ADH1, ADH4, and ADH5, utilizing NADH as a reducing cofactor [49]. Additionally, anaerobic microorganisms can express coenzyme-A-linked acetaldehyde dehydrogenase activities to catalyze reactions involving acetaldehyde and acetyl-CoA [35].

In metabolic engineering, multi-enzyme cascades can be designed to incorporate acetaldehyde elimination systems to optimize the production of target metabolites, such as in cascades designed to improve the production of beta-hydroxy-alpha-amino acids [182]. Furthermore, because the fermentative conversion of pyruvate to acetaldehyde and subsequently to ethanol consumes reducing equivalents and dissipates energy, downregulating the expression of genes in this pathway (such as pyruvate decarboxylase and alcohol dehydrogenases) serves as a key strategy to redirect precursor and cofactor flux toward overexpressed biosynthetic pathways for high-value target compounds [49].