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Kmmig1  as a disrupted mutant of  MIG1  encoding a regulator for glucose repression in  Kluyveromyces marxianus  exhibits a histidine-auxotrophic phenotype. Genome-wide expression analysis revealed that only  HIS4  in seven  HIS  genes for histidine biosynthesis was down-regulated in  Kmmig1 . Consistently, introduction of  HIS4  into  Kmmig1  suppressed the requirement of histidine. Considering the fact that His4 catalyzes four of ten steps in histidine biosynthesis,  K .  marxianus  has evolved a novel and effective regulation mechanism via Mig1 for the control of histidine biosynthesis. Moreover, RNA-Seq analysis revealed that there were more than 1,000 differentially expressed genes in  Kmmig1 , suggesting that Mig1 is directly or indirectly involved in the regulation of their expression as a global regulator.

MIG1 as a positive regulator for the histidine biosynthesis pathway and as a global regulator in thermotolerant yeast Kluyveromyces marxianus