Yichao Cheng, Xinyi Wang, Di Wu, Yao Lu, Yi Qin, Yanlin Liu, Yanying Liang, Yuyang Song
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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 <i>P. kudriavzevii</i> 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 <i>GPD1</i>, <i>PISD</i><i>, </i><i>HIS1</i> and <i>RPIA</i> gene expressions in glycerophospholipid metabolism and the down-regulated <i>FBP1</i>, <i>MDH</i>, <i>IDH3</i>, <i>ICL1</i>, <i>ACL</i> and <i>JEN1</i> gene expressions in carbon metabolism and the biosynthesis pathways of secondary metabolites. Meantime, glucose regulated the expression of transcription factors (e.g., <i>MIG1</i> and <i>GCN4</i>) 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 <i>P. kudriavzevii</i>.</p><p>• <i>Metabolic changes of P. kudriavzevii cells responding to carbon sources were observed</i></p><p>• <i>Potential genes regulating citric acid degradation contributing to CCR were screened</i></p><p>• <i>The inhibition of citric acid degradation is due to changes in the regulatory network</i></p>","PeriodicalId":8342,"journal":{"name":"Applied Microbiology and Biotechnology","volume":"109 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00253-025-13590-3.pdf","citationCount":"0","resultStr":"{\"title\":\"Multi-omics reveals glucose repression of citric acid catabolism in Pichia kudriavzevii\",\"authors\":\"Yichao Cheng, Xinyi Wang, Di Wu, Yao Lu, Yi Qin, Yanlin Liu, Yanying Liang, Yuyang Song\",\"doi\":\"10.1007/s00253-025-13590-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><i>Pichia kudriavzevii</i> 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 <i>P. kudriavzevii</i>. 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 <i>P. kudriavzevii</i> 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 <i>GPD1</i>, <i>PISD</i><i>, </i><i>HIS1</i> and <i>RPIA</i> gene expressions in glycerophospholipid metabolism and the down-regulated <i>FBP1</i>, <i>MDH</i>, <i>IDH3</i>, <i>ICL1</i>, <i>ACL</i> and <i>JEN1</i> gene expressions in carbon metabolism and the biosynthesis pathways of secondary metabolites. Meantime, glucose regulated the expression of transcription factors (e.g., <i>MIG1</i> and <i>GCN4</i>) associated with three pathways, which were crucial genes of CCR regulatory networks. 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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.
• 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
期刊介绍：
Applied Microbiology and Biotechnology focusses on prokaryotic or eukaryotic cells, relevant enzymes and proteins; applied genetics and molecular biotechnology; genomics and proteomics; applied microbial and cell physiology; environmental biotechnology; process and products and more. The journal welcomes full-length papers and mini-reviews of new and emerging products, processes and technologies.
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