Metabolic engineering of Saccharomyces cerevisiae for production of butanol isomers

• Butanol isomers are regarded as superior next-generation biofuels.
• Many pathways can be harnessed for butanol production.
• Baker's yeast is an excellent chassis for industrial production of biobutanol.
• Sophisticated metabolic engineering is needed to obtain highly productive strains.

Saccharomyces cerevisiae has decisive advantages in industrial processes due to its tolerance to alcohols and fermentation conditions. Butanol isomers are considered as suitable fuel substitutes and valuable biomass-derived chemical building blocks. Whereas high production was achieved with bacterial systems, metabolic engineering of yeast for butanol production is in the beginning. For isobutanol synthesis, combination of valine biosynthesis and degradation, and complete pathway re-localisation into cytosol or mitochondria gave promising results. However, competing pathways, co-factor imbalances and FeS cluster assembly are still major issues. 1-Butanol production via the Clostridium pathway seems to be limited by cytosolic acetyl-CoA, its central precursor. Endogenous 1-butanol pathways have been discovered via threonine or glycine catabolism. 2-Butanol production was established but was limited by B12-dependence.

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