2020/01/16 by Chuanbo Zhang, Man Li, Guang-Rong Zhao +1 · 14 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Plant biochemistry and biosynthesis #Microbial Metabolic Engineering and Bioproduction #Microbial Natural Products and Biosynthesis
paper · doi:10.1021/acs.jafc.9b07290
Metabolic engineering of Saccharomyces cerevisiae focusing on the cytoplasm for sustainable terpenoid production is commonly practiced. However, engineering organelles for terpenoid production is rarely reported. Herein, peroxisomes, together with the cytoplasm, were engineered to boost sesquiterpene α-humulene synthesis in S. cerevisiae. The farnesyl diphosphate synthetic pathway and α-humulene synthase were successfully expressed inside yeast peroxisomes to enable high-level α-humulene production with glucose as the sole carbon source. With the combination of peroxisomal and cytoplasmic engineering, α-humulene production was increased by 2.5-fold compared to that in cytoplasm-engineered recombinant strains. Finally, the α-humulene titer of 1726.78 mg/L was achieved by fed-batch fermentation in a 5 L bioreactor. The strategy presented here offers an efficient method for terpenoid production in S. cerevisiae.