At the BI 6727 same time, RAP1 and FHL1 also showed repressed expression response. Deletion mutation response to HMF All selective single gene deletion mutations displayed normal growth similar to their parental strain in the absence of HMF treatment on SC medium. In the presence of HMF, the parental strain BY4742 showed a delayed growth response on SC medium. In contrast, all tested deletion mutations for genes YAP1, RPN4, PDR1, PDR3, YAP4, YAP5, YAP6, ADH6, ADH7, ALD4, SNQ2, ICT1, SHP1, OTU1, MET3, MET14, CHA1, ALT1, SSA4, OYE3, NPL4, MAG1, GRE2, GRE3, ARI1, YBR062C, and YER137C, displayed varied lengths of lag phase. These represent growth defects at different levels in the absence of the individual genes. Among which, the most profound effect was observed by rpn4 and yap1 for transcription factor genes RPN4 and YAP1 as mentioned above.

Metabolic conver sion profiles were highly consistent with the growth response. As assayed by HPLC, no glucose consumption was observed for all tested strains during the lag phase. Discussion Yeast adaptation to lignocellulose derived inhibitor stress is manifest at genome level and likely during the lag phase. Variation in the length of the lag phase has been widely used to measure the tolerance of strains to a specific inhibitor. Using DNA 70 mer long oligo microarray and qRT PCR assays, we investigated com parative transcriptome profilings of S. cerevisiae during the lag phase under HMF challenge in a time course study.

Our comprehensive analyses uncovered important transcription factor genes, including YAP1, YAP5, YAP6, PDR1, PDR3, RPN4, and HSF1, as key regulators for the yeast adaptation, as well as their co regulation and com plicated regulatory networks with numerous multiple function genes. We identified more than 300 genes showing statistically significant differential expression responses that potentially affect yeast adaptation to the inhibitor challenge. Among which, more than 70 genes were consistently induced and more than 200 genes were repressed at varied stages during the lag phase. This is the first report of systematic analysis on genomic expression to inhibitor stress during the lag phase in the context of yeast adaptation. Knowledge obtained from this study provides insight into global adaptive responses of the yeast to inhibitor stress and aids the dissection of tolerance mechanisms of the yeast. Our studies Cilengitide uncovered at least three significant ele ments for yeast adaptation to inhibitor stress and mechanisms of tolerance. The first component involves the functional enzymes and related regulatory networks directly involved in biotransformation and inhibitor out that multiple functions of a gene are common and the co regulation can be a reflection of the multi functions.