Secretory Production of Tocotrienols in Saccharomyces cerevisiae

Tocotrienols as important components of vitamin E have attracted increasing attention, with recent progress made in their heterologous biosynthesis, but all as intracellular products. Aiming to further improve the tocotrienol production capacity of engineered yeast and to advance toward industrial fermentation of tocotrienols, we first optimized the synthetic pathway to enhance the tocotrienol yield and then attempted to realize their secretory production by exploring biphasic extractive fermentation conditions and screening for endogenous transporters. Finally, a Saccharomyces cerevisiae strain with tocotrienol yield of 25.57 mg/g dry cell weight was generated, and the tocotrienol titer reached 82.68 mg/L in shake-flask cultures, with 73.66% of the product secreted into the organic phase. For the first time, we have reported that the vitamin E components could be harvested as extracellular products of microbial cell factories, which could largely simplify the downstream process and could be of significance for fermentative production of these products.