Multi-omics reveals glucose repression of citric acid catabolism in Pichia kudriavzevii.

Pichia kudriavzevii is a widely used yeast in the wine industry that can degrade citric acid. However, this process can be hindered by the presence of glucose through a phenomenon called carbon catabolite repression (CCR). Herein, this study determined the underlying mechanism by examining the effects of glucose on P. kudriavzevii. Our findings indicated that glucose inhibited the reduction of citric acid and maintained elevated levels of fatty acids and glycerophospholipids. However, the inhibition of citric acid degradation under glucose addition was related to the retarded accumulation of metabolites involved in the biosynthesis of antibiotics, propanoate metabolism, microbial metabolism in diverse environments, C5-branched dibasic acid metabolism, and metabolic pathways in diverse environments. Additionally, the integrated data revealed that citrate catabolism of P. kudriavzevii was remarkably repressed in response to glucose by regulating glycerophospholipid metabolism, carbon metabolism and the biosynthesis pathways of secondary metabolites. Further investigations indicated that the increase of fatty acids (e.g., alpha-linolenic and arachidic) and glycerophospholipids (e.g., dihydroxyacetone phosphate and glycerophosphocholine) under glucose addition was related to the up-regulated GPD1, PISD, HIS1 and RPIA gene expressions in glycerophospholipid metabolism and the down-regulated FBP1, MDH, IDH3, ICL1, ACL and JEN1 gene expressions in carbon metabolism and the biosynthesis pathways of secondary metabolites. Meantime, glucose regulated the expression of transcription factors (e.g., MIG1 and GCN4) associated with three pathways, which were crucial genes of CCR regulatory networks. Overall, we uncovered the metabolic regulatory network through which CCR inhibits citric acid utilization in P. kudriavzevii. KEY POINTS: • Metabolic changes of P. kudriavzevii cells responding to carbon sources were observed • Potential genes regulating citric acid degradation contributing to CCR were screened • The inhibition of citric acid degradation is due to changes in the regulatory network.