Genomic and transcriptomic analysis screening key genes for (+)-valencene biotransformation to (+)-nootkatone in Yarrowia lipolytica

Yarrowia lipolytica is a kind of unconventional yeast, which is widely used in food industry because of its safety. (+)-Nootkatone, the ketone derivatives of (+)-valencene, possesses typical grapefruit aroma and is used as aromatics and medicines. It was found that Yarrowia lipolytica was an efficient biocatalyst for the transformation of (+)-valencene to (+)-nootkatone. Thus, it was meaningful to explore the genome features and the gene expression differences of strain Yarrowia lipolytica during (+)-valencene biotransformation, and to study the detailed bioconversion pathways. The results showed that the Yarrowia lipolytica genome was about 20.49 Mb, which encoded 6 137 protein coding genes. There were 1 167 differentially expressed genes (DEGs) in Y_V_36h ((+)-valencene-treated condition) compared to Y_36h ((+)-valencene-untreated blank). During biotransformation, the expression of genes related to the biosynthesis of secondary metabolites and most of ATP-binding cassette (ABC) transporters were significantly up-regulated. In addition, the expression of genes involved in energy metabolism decreased. Moreover, the enzymes participated in (+)-valencene biotransformation were inducible and they were inhibited by cytochrome P450 inhibitors. Several differentially expressed genes related to cytochrome P450 and dehydrogenase (gene2800, gene2911 and gene3152) were significantly up-regulated and might be responsible for converting (+)-valencene to (+)-nootkatone. The RT-qPCR experiment of ten DEGs were further verified and confirmed the reliability of transcriptome results. This study provided a basis for exploring the related genes and molecular regulatory mechanism of (+)-nootkatone biosynthesis from (+)-valencene by Yarrowia lipolytica.

Automated summary

Yarrowia lipolytica is an unconventional yeast widely used in the food industry for its safety, and was found to be an efficient biocatalyst for transforming (+)-valencene into (+)-nootkatone. During this transformation, genes related to secondary metabolite biosynthesis and ATP-binding cassette transporters were up-regulated, while genes involved in energy metabolism were down-regulated. Several differentially expressed genes, such as cytochrome P450 and dehydrogenase, were identified to be responsible for the biotransformation process.