The Dual Role of Pho4 in the Environmental Stress Adaptation of Komagataella phaffii a l'estrès ambiental
The study identifies two Pho4 transcription factors with complementary functions
The transcription factor Pho4 is crucial for the response to phosphate starvation in many fungi, and it has been linked to pathogenicity. Although it is widely accepted that it is encoded by a single gene, scientists at the IBB’s Yeast Molecular Laboratory have reported in two consecutive papers that the yeast Komagataella phaffii (Pichia pastoris) encodes two functional Pho4 proteins (Pho4(A) and Pho4(B)). While Pho4(B) plays a major role in the adaptation to phosphate starvation, Pho4(A) is important for adaptation to alkaline pH. Phenotypic and transcriptomic studies revealed that both transcription factors display partially overlapping functions, respond differently to diverse stimuli, and together constitute a key component in the adaptation to multiple stresses. Pho4-regulated genes, such as PHO89, have been successfully used to drive the expression of industrially relevant proteins in K. phaffii both under Pi limitation and alkalinization of the medium. Therefore, understanding how Pho4 transcription factors are regulated will help to set the basis for the development of improved protein expression platforms.
Articles data:
Albacar M, González A, Wang R, Casamayor A, Ariño J. Komagataella phaffii Encodes Two Functional Pho4 Transcription Factors. International Journal of Molecular Sciences. 2026; 27(15):6561.
Albacar M, Casamayor A, Wang R, Ariño J, González A. The transcriptional response to environmental alkalization involves both Komagataella phaffii Pho4 transcription factors. Microb Cell Fact. 2026 Jul 4. Epub ahead of print.