The general regulators TUP1 and SNF1 are not essential for regulation by glucose of the major genes involved in methanol metabolism from Hansenula poymorpha
Hansenula polymorpha is a methylotrophic yeast widely employed in biotechnology as a “protein factory”. Most promoters used for heterologous protein expression, like MOX(methanol oxidase) and DAS(di-hydroxy acetone synthase), are involved in the peroxisomal methanol metabolism (C1 metabolism) and are under strong glucose repression. Interestingly, the MOXpromoter is subjected to glucose regulation also in Saccharomyces cerevisiae, a non-methylotrophic yeast in which this phenomenon is well studied. In this species, the transcription factor Tup1p plays an essential role in glucose repression of several genes. This effect is counteracted by the activator Snf1p when glucose is exhausted from medium. Therefore, to test whether this regulatory circuit has been conserved in H. polymorpha, HpTUP1and Hp SNF1were partially cloned and disrupted. Deletion of Hp TUP1did not affect glucose repression of the major C1metabolism genes ( MOX, DAS). Thus, though conserved, Hp TUP1does not seem to take part in a general glucose repression in H. polymorpha. In contrast, the deletion of Hp SNF1 led to significant decreases in the activation of these genes in the absence of glucose. Therefore, the effect of Hp SNF1 in transcriptional activation may be through an Hp TUP1- independent circuit.

Apoio financeiro: FAPESP


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