Utilization of n-alkane and roles of lipid transfer proteins in Yarrowia lipolytica

Abstract

Yarrowia lipolytica, a dimorphic yeast belonging to the Ascomycota, has potent abilities to utilize hydrophobic compounds, such as n-alkanes and fatty acids, as carbon and energy sources. Yarrowia lipolytica can synthesize and accumulate large amounts of lipids, making it a promising host to produce various lipids and convert n-alkanes to useful compounds. For advanced use of Y. lipolytica in these applications, it is necessary to understand the metabolism of these hydrophobic compounds in this yeast and the underlying molecular mechanisms. In this review, current knowledge on the n-alkane metabolism and how this is regulated in Y. lipolytica is summarized. Furthermore, recent studies revealed that lipid transfer proteins are involved in the utilization of n-alkanes and the regulation of cell morphology in response to n-alkanes. This review discusses the roles of membrane lipids in these processes in Y. lipolytica.

Keywords: Dimorphism; Fatty acid; Lipid transfer protein; Yarrowia lipolytica; n-Alkane.

Fig. 1

Metabolic pathway of n-alkane and triacylglycerol and transcription regulation of n-alkane metabolism in Y. lipolytica. A Metabolic pathway of n-alkane and triacylglycerol in Y. lipolytica. n-Alkanes are hydroxylated to fatty alcohols by cytochrome P450ALK belonging to the CYP52-family. Fatty alcohols are oxidized to fatty aldehydes by fatty alcohol dehydrogenase or P450ALK in the ER, or by fatty alcohol oxidase in the peroxisome. Roles of Fadh and P450ALK in the oxidation of fatty alcohol remain to be elucidated. Fatty aldehydes are oxidized to fatty acids by fatty aldehyde dehydrogenase in the ER or the peroxisome. Localization of Hfd4 remains unclear. Fatty acids are activated to acyl-CoAs by acyl-CoA synthetase, and are metabolized through β-oxidation pathway in the peroxisome or utilized for membrane or storage lipid synthesis in the ER. Triacylglycerol is hydrolyzed to glycerol and fatty acids by lipase. Fatty acids are incorporated and converted to acyl-CoAs by acyl-CoA synthetase, and metabolized or used for lipid synthesis. B Model of transcriptional regulation of n-alkane metabolism Y. lipolytica. Left: In the absence of n-alkanes, the transcription repressor Yas3p binds to the activator complex composed of Yas1p and Yas2p in the nucleus, and ARE1-dependent transcription is repressed. Right: In the presence of n-alkanes, Yas3p is sequestered to the ER via interaction with PA and/or PIP, and ARE1-dependent transcription is activated

Fig. 2

Model of the function of Sec14-family protein and phylogenetic tree of Sec14-family proteins of S. cerevisiae, C. albicans, and Y. lipolytica. A Model of the function of Sec14-family protein. Left panel, Sec14-family protein transports lipids between membranes. Right panel, Sec14-family protein presents PI to PI kinase to produce phosphoinositide. See text in detail. B The phylogenetic tree of Sec14-family proteins of S. cerevisiae (Sc), C. albicans (Ca), and Y. lipolytica (Yl) was constructed using MEGAX. The scale bar denotes 0.2 substitutions per site. The bootstrap frequencies are indicated. The accession numbers of sequences from UniProtKB are as follows: Sec14 (P24280), Sfh1 (P33324), Sfh2 (Q06705), Sfh3 (P53860), Sfh4 (P53844), and Sfh5 (P47008) of S. cerevisiae, Sec14 (P46250), C6_03470W (A0A1D8PQ60), Pdr16 (A0A1D8PD50), Pdr17 (A0A1D8PGP3), and Sfh5 (A0A8H6BRU9) of C. albicans, and Sec14 (P45816), Sfh21 (Q6CBL6), Sfh22 (Q6C4V3), Sfh23 (Q6CCY6), Sfh24 (Q6C4B2), Sfh3 (Q6CHI5), Sfh51 (Q6C1G2), and Sfh52 (Q6C9R9) of Y. lipolytica

Fig. 3

Phylogenetic tree of ORPs of S. cerevisiae, C. albicans, and Y. lipolytica and structures of ORPs of Y. lipolytica. A The phylogenetic tree of ORPs of S. cerevisiae (Sc), C. albicans (Ca), and Y. lipolytica (Yl) was constructed using MEGAX. The scale bar denotes 0.2 substitutions per site. The bootstrap frequencies are indicated. The accession numbers of sequences from UniProtKB are as follows: Osh1 (P35845), Osh2 (Q12451), Osh3 (P38713), Osh4 (P35844), Osh5 (P35843), Osh6 (Q02201), and Osh7 (P38755) of S. cerevisiae, C1_08180C (A0A1D8PE79), Osh3 (Q59TM0), C2_05720C (A0A1D8PHG1), and OBPA (A0A8H6F3A4) of C. albicans, and Osh1p (Q6C1E8), Osh3p (Q6C4Y2), Osh4p (Q6CC78), and Osh6p (Q6CI24) of Y. lipolytica. B Structures of ORPs of Y. lipolytica. Oxysterol-binding protein domain, Pleckstrin homology domain, FFAT motif, Ankyrin repeat, and GOLD domain are shown