Molecular Basis of Methanol-Inducible Gene Expression and Its Application in the Methylotrophic YeastCandida boidinii

Methanol is a promising feedstock for biotechnological and chemical processes as well as a primary source of energy to replace coal and petroleum. Methylotrophic yeasts, that can utilize methanol as the sole source of carbon and energy, have been studied intensively in terms of both physiological activities and potential applications. During growth on methanol, the enzymes involved in methanol metabolism are massively produced in these yeasts, indicating that the gene promoters of these enzymes are strong methanol-inducible promoters. Using these promoters, high-level heterologous gene expression systems have been developed in several methylotrophic yeast strains, such as Pichia pastoris, Hansenula polymorpha, and Candida boidinii. To achieve efficient industrial use of methanol and efficient protein production by methylotrophic yeasts, it is important to elucidate the molecular basis of methanol-inducible gene expression in these yeasts. This review describes recent advances in understanding of the regulation of methanol-inducible gene expression and the molecular mechanism of transcriptional activation in the methylotrophic yeast C. boidinii. Application of this gained knowledge led to successful production of useful enzymes in this yeast, which is also reviewed.