Details

Autor(en) / Beteiligte

• Lee, Ye‐Gi
• Kim, Chanwoo
• Sun, Liang
• Lee, Tae‐Hee
• Jin, Yong‐Su

Titel

Selective production of retinol by engineered Saccharomyces cerevisiae through the expression of retinol dehydrogenase

Ist Teil von

• Biotechnology and bioengineering, 2022-02, Vol.119 (2), p.399-410

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Retinol is a fat‐soluble vitamin A that is widely used in the food and pharmaceutical industries. Currently, retinol is commercially produced by chemical synthesis. Microbial production of retinol has been alternatively explored but restricted to a mixture of retinoids including retinol, retinal, and retinoic acid. Thus, we introduced heterologous retinol dehydrogenase into retinoids mixture‐producing Saccharomyces cerevisiae for the selective production of retinol using xylose. Expression of human RDH10 and Escherichia coli ybbO led to increase in retinol production, but retinal remained as a major product. In contrast, S. cerevisiae harboring human RDH12 produced retinol selectively with negligible production of retinal. The resulting strain (SR8A‐RDH12) produced retinol only. However, more glycerol was accumulated due to intracellular redox imbalance. Therefore, Lactococcus lactis noxE coding for H2O‐forming NADH oxidase was additionally introduced to resolve the redox imbalance. The resulting strain produced 52% less glycerol and more retinol with a 30% higher yield than a parental strain. As the produced retinol was not stable, we examined culture and storage conditions including temperature, light, and antioxidants for the optimal production of retinol. In conclusion, we achieved selective production of retinol efficiently from xylose by introducing human RDH12 and NADH oxidase into S. cerevisiae. While microbial production of retinol is feasible via metabolic engineering, resulting engineered microorganisms co‐produced retinol with substantial amounts of retinal. In this study, we demonstrate that human retinol dehydrogenase (RDH12) can enable selective production of retinol with negligible production of retinal in engineered yeast.