Recombinant Expression of Aldehyde Dehydrogenase 2 (ALDH2) in Escherichia coli Nissle 1917 for Oral Delivery in ALDH2-Deficient Individuals

Ho, T.; Chang, C.; Wu, J.; Huang, I.; Tsai, L.; Lin, J.; Tai, E.; Chou, C.; Yang, J.; Wei, Y.; Yeh, C.; Chen, W.; Lu, D.; Su, L.; Chang, N.; Huang, C.; Wang, C.; Abrena, P.; Cheung, C.; Whiteford, S.; Chen, P.; Huang, A.; Wu, A.; Wei, B.; Kao, E.; Lin, N.; Chang, A.; Lin, Y.; Tsao, S.; Ward, N.; Chiang, T.; Clapper, J.

doi:10.1101/674606

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bioRxiv · 10.1101/674606

Recombinant Expression of Aldehyde Dehydrogenase 2 (ALDH2) in Escherichia coli Nissle 1917 for Oral Delivery in ALDH2-Deficient Individuals

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Abstract

Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, this flushing response is caused by an accumulation of acetaldehyde, a carcinogenic intermediate of alcohol metabolism. Aldehyde dehydrogenase 2 (ALDH2) deficiency, the result of a point mutation, produces a less efficient ALDH2. The resulting accumulation of acetaldehyde greatly increases the risk of developing esophageal and head and neck cancers. In this study, we produced recombinant ALDH2 in the probiotic E. coli Nissle 1917, which successfully reduces acetaldehyde levels in simulated oral conditions. Packaged in a hard candy, the ALDH2-probiotic would remain in the mouth to specifically target salivary acetaldehyde. Using mathematical modeling, we also determined how much recombinant ALDH2 is needed to reduce elevated acetaldehyde levels.\n\nFinancial DisclosureThis work was funded by Taipei American School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\nCompeting InterestsThe authors have declared that no competing interests exist.\n\nEthics StatementN/A\n\nData AvailabilityYes - all data are fully available without restriction. Sequences for the plasmids used in this study are available through the Registry of Standard Biological Parts. Links to raw data are included in Supplementary Information.

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Ho, T., Chang, C., Wu, J., Huang, I., Tsai, L., Lin, J., Tai, E., Chou, C., Yang, J., Wei, Y., Yeh, C., Chen, W., Lu, D., Su, L., Chang, N., Huang, C., Wang, C., Abrena, P., Cheung, C., Whiteford, S., Chen, P., Huang, A., Wu, A., Wei, B., Kao, E., Lin, N., Chang, A., Lin, Y., Tsao, S., Ward, N., Chiang, T., Clapper, J.. 2019-06-21. Recombinant Expression of Aldehyde Dehydrogenase 2 (ALDH2) in Escherichia coli Nissle 1917 for Oral Delivery in ALDH2-Deficient Individuals. https://doi.org/10.1101/674606

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