Gene Circuit Construction and Simulation in Probiotics to Metabolize Alcohol

Abstract

Flushing response after alcohol consumption is common in East Asia, caused by alcohol enzyme deficiency. Alcohol dehydrogenase (ADH), the major enzyme in alcohol metabolism pathways, are deficient to dissolve alcohol. People with decreased numbers and activity of enzymes are at higher risks of esophageal cancers. However, there is a lack of alcohol degrading products and relevant researches to address the issue in the current market. Although there are commercially available products to relieve symptoms and protect patients’ liver, none of them are dedicated to primarily enhancing enzyme activity for more efficient clearance of alcohol. Therefore, our research aims to offer a synthetic-biology solution for people with ADH deficiency to metabolize alcohol efficiently and reduce negative health effects. To do this, we took a two-step approach. First, we did computational analysis on designing and engineering three genetic circuits that can produce the most ADH in an alcohol-rich environment. This provides a great opportunity for ADH to degrade alcohol. Furthermore, we investigated different circuit dynamics under different drinking patterns (e.g., fast drinker, slow drinker, etc.) and were able to recommend customized circuit based on different situations. Second, we conducted basic laboratory experiments to select probiotic strain for future engineering purposes. Namely, we cultured Escherichia. Coli, Bacillus subtilis, Lactobacillus delbrueckii subsp. Bulgaricus, and Streptococcus thermophilus under different concentrations of alcohol to select the most alcohol-tolerant probiotic. Overall, our research develops an engineered probiotic system in which the gene circuit can efficiently decay alcohol based on various drinking patterns.