Enhanced Isoprene Production by Reconstruction of Metabolic Balance between Strengthened Precursor Supply and Improved Isoprene Synthase in Saccharomyces cerevisiae

ACS Synthetic Biology
Zhen YaoHongwei Yu

Abstract

Isoprene, as a versatile bulk chemical, has wide industrial applications. Here, we attempted to improve isoprene biosynthesis in Saccharomyces cerevisiae by simultaneous strengthening of precursor supply and conversion via a combination of pathway compartmentation and protein engineering. At first, a superior isoprene synthase mutant ISPSLN was created by saturation mutagenesis, leading to almost 4-fold improvement in isoprene production. Subsequent introduction of ISPSLN to strains with strengthened precursor supply in either cytoplasm or mitochondria implied an imperfect match between the synthesis and conversion of the isopentenyl pyrophosphate (IPP)/dimethylallyl diphosphate (DMAPP) pool. To reconstruct metabolic balance between the upstream and downstream flux, additional copies of diphosphomevalonate decarboxylase gene ( MVD1) and isopentenyl-diphosphate delta-isomerase gene ( IDI1) were introduced into the cytoplasmic and mitochondrial engineered strains. Finally, the diploid strain created by mating the above haploid strains produced 11.9 g/L of isoprene, the highest ever reported in eukaryotic cells.

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Citations

Jan 1, 2021·Frontiers in Bioengineering and Biotechnology·Jiwon KimSun-Mi Lee
Jan 17, 2021·Applied and Environmental Microbiology·Jared AldridgeNicole R Buan
Aug 28, 2020·Current Opinion in Biotechnology·Yuexuan ZuGregory Stephanopoulos
Jul 9, 2021·International Journal of Biological Macromolecules·Yuru TongWei Gao
Aug 12, 2021·Journal of Agricultural and Food Chemistry·Jie MaiXiao-Jun Ji
Aug 10, 2021·Biotechnology Progress·Kurshedaktar M Shaikh, Annamma A Odaneth
Jan 29, 2020·Journal of Agricultural and Food Chemistry·Tian LiDong-Zhi Wei

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