Kluyveromyces marxianus strain:FIM1 Raw sequence reads

In yeast strains for producing recombinant protein, cells experience high production related stresses similar to high temperatures. It is possible to increase recombinant protein production by enhancing thermotolerance. We isolated a heat resistant Kluyveromyces marxianus strain FDHY23 from the original strain FIM1 through high temperature screening. It also exhibited enhanced recombinant protein productivity at both room and high temperatures. Based on DNA sequencing, the CYR1N1546K mutation was identified as responsible for the improved phenotype. Introducing this mutation into the wild strain greatly enhanced both thermotolerance and recombinant protein yields. RNA sequencing revealed that under high temperature and recombinant protein production conditions, CYR1 mutation induced reduction in cAMP levels can stimulate cells to improve its energy supply system and optimize material synthesis, meanwhile enhance stress resistance, based on the altered cAMP signaling cascades. Our study provides CYR1 mutation as a novel target to overcome the bottleneck in achieving high production of recombinant proteins under high temperature conditions, and also offer a convenient approach for high-throughput screening of recombinant proteins with high yields.