Cleaner Production of Natamycin from Lignocellulosic Hydrolysates via a Semi-solid-state Fermentation Based on Porous Materials

Abstract Natamycin is primarily produced via submerged fermentation (SmF), a process often limited by inefficient oxygen transfer, high agitation energy consumption, and the generation of substantial organic wastewater. This study introduces a semi-solid-state fermentation (SSSF) strategy using perlite carriers and corn straw hydrolysates (CSH) based substrates to enhance natamycin production. Under optimized conditions, 40% medium saturation, inoculation with 2.0 × 109 spores/L, 26 °C, and atomized nutrient supplementation, the SSSF process yielded 15.6 g/L of natamycin after 7 days, achieving a productivity of 2.2 g/L/day. The improvement is attributed to a more natural habitat that facilitates direct oxygen and nutrient transfer to the cells, accompanied by upregulated transcription of key biosynthetic genes, enhanced enzyme activity, improved energy metabolism, expanded pools of precursor metabolites, and strengthened antioxidative capacity. Owing to these advantages, SSSF reduced the total natamycin production cost by 83%, while eliminating fermentative wastewater and increasing natamycin productivity 2.9-fold versus glucose-based SmF. The SSSF strategy enables efficient natamycin biosynthesis with reduced energy input and no wastewater generation, demonstrating strong potential for industrial-scale application.