Renewable, high-performance Sustainable Aviation Fuel (SAF) is essential to the future of aviation and to meeting the airline industry commitment of a 50% reduction in 2050 GHG emissions compared to 2005. This important commitment necessitates large-scale liquid fuel production from non-petrochemical sources that yield fuels still adhering to industrial fuel standards. Recently, the US Navy has identified a promising aviation biofuel blendstock, 1,4-dimethylcyclooctane (DMCO). DMCO can be produced by a chemical route (dimerization and subsequent hydrogenation) from isoprene, but biological production of isoprene has a high risk of explosion under aerobic conditions and product recovery challenges. In order to circumvent the challenges, isoprenol (3-methyl-3-buten-1-ol) has been proposed and tested as a more suitable precursor of DMCO for large-scale production. Isoprenol has been produced from engineered E. coli strain with heterologous mevalonate (MVA) pathway, but toxicity of the key intermediate isopentenyl diphosphate (IPP) has been a significant bottleneck of high titer production of isoprenol in microbial hosts. To address this issue, we have developed an IPP-bypass pathway for isoprenol production and recently achieved 10.8 g/L of isoprenol titer from E. coli in a 2-L fed-batch fermentation. E. coli, however, may not be an ideal industrial host for the further commercialization of isoprenol. Saccharomyces cerevisiae, on the other hand, is a more favored microbial cell factory considering its inherent safety, industrial robustness, and ease of genetic manipulation. In this work, we have engineered S. cerevisiae for isoprenol production using both the original MVA pathway and the IPP-bypass pathway. We identified a promiscuous endogenous kinase that could divert the pathway flux from isoprenol production and significantly improved the isoprenol titer by knocking out this gene in yeast. More engineering to improve yeast strain as a promising isoprenol producer for industrial application has been attempted.

Engineering Saccharomyces cerevisiae for isoprenol production, a precursor of sustainable aviation fuel DMCO

ACS Spring 2022

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