Natural products (+)-nootkatone is an important sesquiterpene compound and is widely used in pharmaceutical, cosmetic, agricultural and food industries. The aim of this study was to analyze the differentially expressed proteins (DEPs) during citrus aroma compound (+)-valencene biotransformation to (+)-nootkatone by Yarrowia lipolyticaby with high-throughput LC-MS/MS. A total of 778 proteins were differentially expressed, 385 DEPs were significantly up-regulated and 393 DEPs were markedly down-regulated. It was found that the enzymes transformed (+)-valencene to (+)-nootkatone were mainly existed in yeast intracellular and precipitated under the condition of 30-40 % ammonium sulfate. Most DEPs involved in amino acid and fatty acid metabolism were down-regulated during (+)-valencene biotransformation. The DEPs related to the carbohydrate metabolism, energy metabolism and most of transporter proteins were significantly up-regulated. Furthermore, the key enzymes involved in (+)-valencene transformation might be related to cytochrome P450s (gene2215 and gene2911) and dehydrogenases (gene6493). This is the first time that proteomics was used to investigate the metabolism mechanism of Yarrowia lipolytica during (+)-valencene biotransformation. The proteomic analysis of Yarrowia lipolytica provided a foundation for the molecular regulatory mechanism in the biotransformation to (+)-nootkatone from (+)-valencene.
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