Media Optimization for Penicillin Production in Penicillium chrysogenum PTCC5031 via Flux Balance Analysis

Mansoubi Hosseini, Masoumeh; Hosseini, Fakhri Sadat; Takfallah, Fatemeh

doi:10.22104/mmb.2026.8032.1191

Media Optimization for Penicillin Production in Penicillium chrysogenum PTCC5031 via Flux Balance Analysis

Document Type : Research Paper

Authors

Masoumeh Mansoubi Hosseini

Fakhri Sadat Hosseini

Fatemeh Takfallah

Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran

10.22104/mmb.2026.8032.1191

Abstract

Penicillium chrysogenum is the principal microorganism used for the industrial production of penicillin. The widespread use of this fungus has led to certain challenges regarding antibiotic production. As the global demand for antibiotics continues to increase, the importance of nutritionally balanced and cost-effective culture media becomes increasingly evident. Traditionally, different optimization methods have been used for culture media, many of which have been useful and improved our current knowledge of the matter. These methods have mostly been based on experimentation and refinement. However, large-scale manufacturing requires higher efficiency in terms of time and resources, as well as higher precision. In recent years, the emergence of modern computational tools such as genome-scale metabolic models (GSMMs) has greatly improved our ability to understand and predict fungal and microbial metabolic behavior, which in turn has led to improvements in the optimization of manufacturing processes. In this study, a GSMM of P. chrysogenum PTCC5031 was used to identify optimal nutrient settings that theoretically enhance penicillin production under defined uptake constraints. The model combined metabolic pathway analysis with flux balance analysis to evaluate different culture conditions. Among the tested conditions, maltotriose and urea were identified as the most effective carbon and nitrogen sources and showed better cellular growth kinetics and higher antibiotic production rates. Further laboratory-scale validation confirmed the predicted qualitative trends, with penicillin titers increasing by up to 11% under optimized sucrose–urea conditions compared to the baseline medium. The findings highlight the utility of GSMM-driven approaches for medium design and optimization. This predictive framework can help reduce costs and accelerate the development process in biomanufacturing and biotechnology.

Keywords

Genome-scale metabolic model

Fermentation optimization

Nutrient configuration

Antibiotic biosynthesis

Subjects

Microbial fermentation and bioprocessing

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