Discovery of mannose as an alternative non-nutrient-deficient regulator of lipid accumulation in microalgae

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INTRODUCTION: Microalgae are considered promising bioenergy producers, but their commercial potential is limited by low lipid yields. Nutrient deprivation, particularly nitrogen starvation, is a primary strategy to enhance lipid synthesis efficiency in microalgae. However, controlling this process flexibly, effectively, and accurately remains challenging. Moreover, nutrient deficiency triggers expression changes of numerous genes, complicating the identification of key lipid biosynthesis regulators. OBJECTIVES: For the first time, we investigated mannose as a novel non-nutrient-deficient regulator of lipid accumulation in microalgae and explored its potential underlying mechanisms. METHODS: We examined how mannose induction affectslipid accumulation in Chlorella sorokiniana W1 under various culture conditions and compared its effects with nitrogen-starvation. Transcriptome analysis and genome-scale metabolic modeling were used to elucidate the regulatory mechanisms underlying mannose-induced lipid synthesis. Additionally, potential transcription factors were identified using weighted gene co-expression network analysis. RESULTS: Mannose drives rapid and sustained lipid accumulation in C. sorokiniana under various cultivation conditions, independent of nutrient deficiencies. Under autotrophic conditions, mannose increased lipid content of microalgae by 80.1 %. Notably, mannose was not consumed during cultivation, supporting its role as an inducer. Transcriptomic analysis revealed that mannose increased carbon flux by upregulating genes associated with the Calvin cycle, glycolysis, the TCA cycle, and starch degradation. It also redirected carbon towards lipid accumulation by upregulating lipid synthesis pathways and downregulating lipid degradation pathways. Additionally, two SBP1 transcription factors specifically responsive to mannose were identified and may regulate carbon metabolism in microalgae. CONCLUSION: Our study introduces mannose as a novel non-nutrient-deficiency regulatory factor for lipid accumulation in C. sorokiniana W1, and explores its metabolic and regulatory mechanisms under various nutrient conditions. The research demonstrates that mannose induction has significant potential for improving microalgal lipid production in practical applications.

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