Abstract
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. 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.
Highlights
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
MEP peak detected in Y. lipolytica was identical to the analytical MEP standard, thereby meeting the criteria for metabolite identification based on The Metabolomics Standards Initiative (MSI) for level 1 identification (Fig. 2)
We hypothesized that Y. lipolytica might utilize an isozyme that catalyzes the DXR-like a ctivity[39,40] or that the MEP found in Y. lipolytica was synthesized by an enzyme with extremely low or no homology with the known enzyme in the MEP pathway
Summary
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. 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. Many studies reported that the MEP pathway does not exist in the yeast, surprisingly, a chromatographic peak annotated as MEP was observed in the intracellular extract of Y. lipolytica cultured in a nitrogen limiting condition. This phenomenon is inconsistent with a conventional understanding regarding isoprenoid biosynthesis in yeast. This study suggested that the MVA and MEP pathways co-exist in Y. lipolytica
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