ReviewBiotechnology letters2026
Challenges, optimization, and delivery strategies in the heterologous expression of aldehyde dehydrogenase: therapeutic applications for acetaldehyde detoxification.
Review in Biotechnology letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The aldehyde dehydrogenase (ALDH) superfamily plays a critical role in acetaldehyde detoxification. The mitochondrial ALDH2 isoenzyme serves as the core enzyme in alcohol metabolism because of its high affinity for acetaldehyde. Loss-of-function mutation (such as ALDH2*2) of the gene is highly prevalent in East Asian populations. These mutations cause acetaldehyde accumulation and significantly increase the risk of alcohol-related diseases. Therefore, it is necessary to develop efficient recombinant ALDH2 supplementation therapies. However, its heterologous expression faces three major bottlenecks: (1) catalytic turnover leading to NAD⁺ depletion; (2) difficulty in functional tetramer assembly; and (3) cytotoxicity of the substrate acetaldehyde, which inhibits cell growth. The review covers rational host selection and multi-level synergistic optimization of transcription, translation, folding, and metabolism. Examples include promoter optimization, codon optimization, terminator optimization, and chaperone co-expression. Ultimately, we explore essential stabilization formulations and innovative delivery strategies, such as nano-encapsulation and engineered probiotics, needed to realize the therapeutic potential of ALDH2. The goal is to promote the industrial production and clinical translation of recombinant ALDH2.
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