Stable isotope and chemical inhibition analyses suggested the existence of a non-mevalonate-like pathway in the yeast Yarrowia lipolytica

Methyl erythritol phosphate (MEP) is the metabolite found in the MEP pathway for isoprenoid biosynthesis, which is known to be utilized by plants, algae, and bacteria. In this study, an unprecedented observation was found in the oleaginous yeast Yarrowia lipolytica, in which one of the chromatographic peaks was annotated as MEP when cultivated in the nitrogen limiting condition. This finding raised an interesting hypothesis of whether Y. lipolytica utilizes the MEP pathway for isoprenoid biosynthesis or not, because there is no report of yeast harboring the MEP pathway. Three independent approaches were used to investigate the existence of the MEP pathway in Y. lipolytica; the spiking of the authentic standard, the MEP pathway inhibitor, and the 13C labeling incorporation analysis. figure1

Fig: Biosynthetic pathways for isoprenoid precursors. The mevalonic acid (MVA) pathway in animals, plants (cytosol), fungi, and archaea. The methylerythritol phosphate (MEP) pathway in eubacteria, green algae, and the plastids of higher plants. Abbreviations: CDP-ME, methylerythritol cytidyl diphosphate; DXP, 1-deoxy-D-xylulose 5-phosphate; DXR, DXP reductoisomerase; DXS, DXP synthase; HMBPP, 4-hydroxy-3-methyl-butenyl-1-diphosphate; IPP, Isopentenyl diphosphate; IDI, IPP:DMAPP isomerase; MEcPP, 2-C-methyl-D-erythritol-2,4-cyclodiphosphate; MK, mevalonic acid kinase; PMD, phospho-mevalonate decarboxylase; PMK, phosphomevalonate kinase; DMAPP, dimethylallyl diphosphate; HMG-CoA, hydroxymethylglutaryl-CoA; MVA, mevalonic acid; MVAP, phosphomevalonic acid; MVAPP, diphosphomevalonic acid.

The study suggested that the mevalonate and MEP pathways co-exist in Y. lipolytica and the nitrogen limiting condition triggers the utilization of the MEP pathway in Y. lipolytica.

 

Dissook, S., Kuzuyama, T., Nishimoto, Y. et al. Stable isotope and chemical inhibition analyses suggested the existence of a non-mevalonate-like pathway in the yeast Yarrowia lipolytica. Sci Rep 11,5598 (2021). https://doi.org/10.1038/s41598-021-85170-0

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