The adaptation of microorganisms to different environmental conditions, such as temperature, salinity, extreme pH values, and oscillation in the availability of nutrients (carbon, nitrogen, and phosphate), has a vital role for their survival. The transduction of the signal generated by the sensing of the extracellular pH by fungi occurs through a conserved molecular pathway that involves the activation of PacC transcription factor. This adaptive response is observed in various species and impacts the metabolic processes, pathogenicity, and biotechnological applications in the industry. Variations in pH can influence nearly all physiological processes that lead to the secretion of macromolecules and metabolites. Under the influence of the regulatory circuits of carbon, nitrogen, sulfur, and pH, the regulation of inorganic phosphate (Pi) uptake is performed by several regulatory genes, such as Nuc-1 transcription factor. Nuc-1 is involved with the post-transcriptional control and regulation of the transcription of structural genes that act in the homeostasis system and Pi uptake. Pi is essential for maintaining cell structure and many metabolic processes, being a growth limiter in nature. Thus, the genetic and molecular mechanisms that control the adaptation of microorganisms to the variations of Pi levels are being shown in many model organisms. In this way, the study of the adaptive microbial response to Pi oscillations has high importance, since these investigations may contribute to portray the regulation of molecular mechanisms involved with the Pi system and pH regulator circuit. The pH regulation, once established, will permit the genetic manipulation of economic and medical processes.