GSE175794
Tryptophan plays a central role in yeast's tolerance to isobutanol
Isobutanol is considered a potential biofuel and can be produced by genetically modified microorganisms. Saccharomyces cerevisiae inherently produces isobutanol through valine intermediate(s), so it serves as a good host. However, isobutanol's toxicity remains a key obstacle for bioproduction. In our study, we first used image recognition to screen the colony growth of a yeast gene deletion library and inferred that genes involved in tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP) contribute to isobutanol tolerance. The importance of tryptophan in yeast's tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in a tryptophan biosynthesis defective strain by adding exogenous tryptophan. Transcriptomic analysis revealed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis defective host were up regulated under conditions such as nitrogen starvation. This may explain why ubiquitination for protein degradation was involved for the protein turnover. PPP metabolites and vitamin B1/B6 may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and antioxidative ability and figured out that tryptophan may play a crucial role on isobutanol tolerance. Our study highlights the central role of tryptophan in yeast's isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance. Overall design: Wild type (WT) and tryptophan synthase (TRP5) defected strain Sc12 was cultured with/without isobutanol and/or tryptophan for 24 hours (n=3).