Response surface methodology optimization of L-arginine deiminase from Penicillium chrysogenum and the influence of phytohormones

Abstract

The study presents an optimization process to produce L-arginine deiminase (ADI) from the fungus Penicillium chrysogenum, focusing on the impact of growth parameters and the role of phytohormones and polyamines. ADI, an enzyme that catalyzes the conversion of L-arginine to citrulline and ammonia, holds potential for cancer therapy by depleting L-arginine into auxotrophic tumors. The research identified optimal conditions for ADI production, including an incubation period of 6 days, 150 rpm agitation, and specific nutrient concentrations, with glucose and yeast extract as preferred carbon and nitrogen sources, respectively. L-arginine enhancement was most effective at pH 6 and 35 °C. Phytohormones such as gibberellic acid (GA3) and polyamines including spermidine and spermine were found to significantly boost enzyme production at lower concentrations. The study employed a Plackett-Burman design to determine critical factors, highlighting pH and glucose concentration as key influencers, supported by statistical analysis and 3D surface plots. These results open the door for the therapeutic synthesis of ADIs on a massive scale, necessitating additional study to maximize these enzymes for use in clinical settings.