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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)399-410
Number of pages12
JournalBiotechnology and bioengineering
Volume119
Issue number2
DOIs
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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