Carbon starvation drives biosynthesis of high mannose-composition polysaccharides in Ganoderma lucidum

Polysaccharides with high mannose composition exhibit favorable antitumor activity, but there is currently a lack of well-defined and practical approaches to efficiently manufacture this type of polysaccharide. This study explores the impact of carbon utilization on exopolysaccharide (EPS) production and monosaccharide composition in Ganoderma lucidum, aiming to promote the biosynthesis of polysaccharides with high mannose composition. Sucrose supply significantly increased the mannose proportion to 35.52 % in EPS via carbon starvation. To enhance polysaccharide production with high mannose composition, a joint control by carbon starvation and glucose feeding strategy was developed, achieving 0.42 g/L EPS and 18.67 % mannose with 5 g/L glucose supplementation on day 6 in an initial 10 g/L glucose medium. Using this approach, G. lucidum mycelia exhibited normal growth patterns similar to those in sucrose culture. Essentially, carbon starvation upregulated key genes in the GDP-mannose synthesis pathway, including phosphomannose isomerase (PMI), phosphomannose mutase (PMM), and GDP-mannose pyrophosphorylase (GMP), by over 2-fold, facilitating high mannose-composition polysaccharide synthesis in both sucrose and carbon starvation conditions. This work provides insights into the biosynthesis of structurally specific polysaccharides in G. lucidum and offers a foundation for developing polysaccharides with diverse applications in food, medicine, and other fields.