INDUCIBLE EXPRESSION OF A HETEROLOGOUS PROTEIN IN HANSENULA-POLYMORPHA USING THE ALCOHOL OXIDASE-1 PROMOTER OF PICHIA-PASTORIS

Pichia pastoris (Pp) and Hansenula polymorpha (Hp) are methylotrophic yeasts commonly used for industrial purposes. Growth of either of thes e yeasts in the presence of methanol as the carbon source results in h igh-level induction of alcohol oxidase expression. The respective alco hol oxidase genes, AOX1 in Pp and MOX in Hp, have similar regulatory c haracteristics. Our studies show that the Pp AOX1 promoter(AOX1p) can be used for methanol-induced expression of a heterologous gene in Hp. Furthermore, the size of an AOX1p-heterologous gene-AOX1 terminator ca ssette transcript synthesized in Hp is indistinguishable from that syn thesized in Pp suggesting that transcription both initiates and termin ates at the same sites in both yeast species. Induction of AOX1p in Hp demonstrates that the methanol-inducible regulatory mechanism in Hp i s able to recognize and activate the Pp promoter in spite of extensive sequence variations between AOX1p and MOXp.