Production of metallothionein in copper- and cadmium-resistant strains of Saccharomyces cerevisiae.

Certain mutants of the yeast Saccharomyces cerevisiae show copper or cadmium resistance. Both copper- and cadmium-resistant strains produce the same metallothionein with 53 amino acid residues which causes metal detoxification by chelating copper or cadmium. The metal detoxification role is the only known function of the metallothionein in yeast. The MT is encoded by the CUP1 gene on chromosome VIII which is expressed by induction with metals. The CUP1 is amplified to 3-14 copies with 2 kb-tandem-repeat units in the metal-resistant strains, whereas the wild-type strain contains only a single copy of the CUP1. Although transcription of CUP1 is inducible by metals, the ACE1 protein serves a dual function as a sensor for copper and an inducer for CUP1 transcription in the copper-resistant strain. In the cadmium-resistant strain, the heat-shock factor having a point mutation may be the regulator for CUP1 transcription. Therefore, it has been clarified that production of MT in yeast is controlled by two systems, the amplification of CUP1 and its transcriptional regulation.