A comprehensive investigation on statistical approaches and classical strain improvement for penicillin V production by Penicillium rubens BIONCL P45 strain

Abstract

Media engineering and strain improvement are critical aspects of microbial biotechnology playing a vital role in enhancing microbial productivity, and ensuring cost-effective bioprocessing. In this investigation, we optimized the various medium components, nutritional condition, and fermentation parameters for the industrial production of phenoxymethylpenicillin or penicillin V (PenV). We have isolated, characterized Penicillium rubens BIONCL P45 strain which initially produced 100 mg/L of PenV. Further, optimization using production medium 4 (PM4) comprising lactose, corn steep solids, sodium sulfate, calcium carbonate, and phenoxy acetic acid lead to a significant increase in production, reaching 430 mg/L. Further improvements through response surface methodology (RSM) predicted a production of 646 mg/L, which was experimentally validated at 685 mg/L. Subsequently, mutagenesis studies using UV (ultraviolet) exposure resulted in the UV-65 mutant, which demonstrated a superior performance, achieving 934 mg/L, surpassing the parental strain. ​These combined strategies lead to a tenfold increase in PenV titer, highlighting their effectiveness in bioprocess development and industrial-scale antibiotic production.

Keywords

Box-Behnken design / Response surface methodology / Media optimization / Penicillium rubens / Penicillin V / Classical strain improvement

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Funding

Council of Scientific and Industrial Research, India(MLP101126)

RIGHTS & PERMISSIONS

Jiangnan University