Komagataella phaffii encodes two Pho4 transcription factors: a comparative functional study under phosphate starvation and high pH stress

The vast majority of fungi encode a single Pho4-encoding gene. However, the genome of the industrially relevant yeast Komagataella phaffii appears to encode two possible Pho4 proteins, namely PAS-chr1-1_0265 and PASchr2-1_0177, designated here PHO4(A) and PHO4(B), respectively, which have never been functionally characterized.

Phenotypic analysis of single and double mutants suggests that Pho4(B) plays a major role in adaptation to Pi scarcity. The phenotypes of single mutants do not overlap, but the double mutant is sensitive to multiple types of stress, including alkaline pH. Transcriptomic analysis under Pi starvation confirms that Pho4(B) is crucial for the typical transcriptional response (induction of PHO5, PHO89, VTC1, etc.).