Optimization of cell growth and carotenoid production of Xanthophyllomyces dendrorhous through statistical experiment design

This study was to identify and optimize the major culture factors for both cell growth and carotenoid biosynthesis in Xanthophyllomyces dendrorhous through statistical experiment design and data analysis. A screening test was first conducted on seven culture factors including pH and six medium components using a Plackett-Burman design, from which glucose, ammonium sulfate and pH were identified as the significant factors affecting both cell growth and carotenoid biosynthesis. These significant factors were optimized by central composite design of experiments and response surface methodology, as 34.3 g/L glucose, 2.95 g/L ammonium sulfate and pH 5.85 for cell growth in the culture, and 19.3 g/L glucose, 0.81 g/L ammonium sulfate and pH 5.19 for carotenoid accumulation in the yeast cells, respectively. Then a two-stage culture process was exercised with these optimal conditions tailored for cell growth (first stage) and carotenoid accumulation (second stage), achieving 95.8% higher volumetric yield (18.6 mg/L versus 9.5 mg/L in the single-stage culture) and 22.6% higher volumetric productivity (2.33 mg/(L day) versus 1.90 mg/(L day)) of total carotenoid. The medium optimization results suggest that carotenoid biosynthesis in X. dendrorhous is promoted by high C/N ratio, low carbon and nitrogen concentrations, and a slightly acidic condition when the cell growth is suppressed.