毕赤酵母甘油-甲醇碳源转换的脂质组学研究

Pichia pastoris is an attractive eukaryotic host widely employed in industrial biotechnology for protein production and biocatalysis, while more physiological parameters during the cultivation cycle needed to be revealed, since oxidative stress and other stress conditions were encountered. The present study aimed to understand the lipid profile change of P. pastoris during cell growth with the carbon source switching from glycerol to methanol. The comparative lipidomics of P. pastoris at different stages (lag, logarithmic, stationary, induction and decline phases) was analyzed by a sensitive ultra-performance liquid chromatography/nanoelectrospray-mass/mass spectrometry. We identified more than 253 lipid species, including glycerophospholipids, glycerolipids and sphingolipids. High diversity and flexibility of lipids (including the composition and relative intensity) were observed during different phases, especially when glycerol was shifted to methanol. Especially, the unsaturated-double-bonds containing lipids showed a close relationship with the change of oxidative stress and changed with the adaptation of P. pastoris cells during the culture period. The increasement of sphingolipids in decline stage could link with cell apoptosis. The current study expanded our understanding of the cell physiology of P. pastoris through the lipid profile change and provided knowledge to chassis design strains by engineering microbial membrane.