Green microalga Chromochloris zofingiensis conserves substrate uptake pattern but changes their metabolic uses across trophic transition

The terrestrial green alga <i>Chromochloris zofingiensis</i> is an emerging model species with potential applications including production of triacylglycerol or astaxanthin. How <i>C. zofingiensis</i> interacts with the diverse substrates during trophic transitions is unknown. To characterize its substrate utilization and secretion dynamics, we cultivated the alga in a soil-based defined medium in transition between conditions with and without glucose supplementation. Then, we examined its exometabolite and endometabolite profiles. This analysis revealed that regardless of trophic modes, <i>C. zofingiensis</i> preferentially uptakes exogenous lysine, arginine, and purines, while secreting orotic acid. Here, we obtained metabolomic evidences that <i>C. zofingiensis</i> may use arginine for putrescine synthesis when in transition to heterotrophy, and for the TCA cycle during transition to photoautotrophy. We also report that glucose and fructose most effectively inhibited photosynthesis among thirteen different sugars. The utilized or secreted metabolites identified in this study provide important information to improve <i>C. zofingiensis</i> cultivation, and to expand its potential industrial and pharmaceutical applications.