THE TALE OF TWO TRANSCRIPTION FACTORS

Pichia pastoris,a methylotrophic yeast, is widely used as a host for the production of a numberof recombinant proteins. Our ownlaboratory had used this strain for the expression of Hepatitis B virus surfaceantigen and these recombinant strainsare now being used for the production of recombinant Hepatitis B vaccine(BEVAC, ELOVAC-B. TRIPVAC-HB). Despiteits extensive use by the global Biotech industry, several basic aspects ofmetabolism as well as gene regulation are not well understood in P.pastoris. Our laboratory has beenstudying transcriptional regulation of the gene encoding Alcohol Oxidase I, thefirst enzyme involved in methanol metabolism. Studies thus far have led to the characterization of two transcriptionfactors, Mxr1p (methanol expression regulator I) and ROP (Repressor ofPhosphoenolpyruvate carboxykinase) which play a key role in the regulation ofgenes of methanol and Biotin metabolism (1-4). The lecture entitled “the tale of two transcription factors” willprimarily discuss the mechanism of transcriptional regulation by Mxr1p and ROPand our attempts to exploit these basic research findings for the developmentof novel P. pastoris strains.