Micronutrients content directly impact cerulenin production by Sarocladium oryzae BRM 59907

Fungal secondary metabolites, renewable compounds with diverse bioactivities, offer potential for medicines, colorants, and agrochemicals. Their biotechnological production bottlenecks, such as low production and variable yield, can be overcome through bioprocess engineering techniques and experimental designs. Cerulenin, a broad-spectrum antimicrobial compound produced by Sarocladium oryzae, can be obtained with higher yields and lower costs using these strategies. In this work, cerulenin production by Sarocladium oryzae BRM 59907 was optimized considering its micronutrient requirements. Plackett-Burman and Doehlert designs showed that magnesium supplementation inhibits cerulenin biosynthesis, while the addition of iron source stimulates it. Thus, it was possible to reach an optimal condition (20 g L⁻¹ glycerol, 5 g L⁻¹ glucose, 2.5 g L⁻¹ peptone, 0.025 g L⁻¹ NaCl, 0.029 g L⁻¹ FeCl₃, 28 ºC and 150 rpm) with a reduction of 74 % in the cerulenin production cost considering only culture medium components from the original condition. Bioprocess scale-up in a bioreactor resulted in a cerulenin productivity of 1.39 mg L⁻¹ h⁻¹ in 72 h. This work presents the first bioprocess that efficiently utilizes glycerol as the primary carbon source for the secondary metabolite production. Magnesium supplementation increased cell growth but inhibited cerulenin production, while iron addition increased the concentration of cerulenin.