01994nas a2200217 4500008004100000022001400041245009600055210006900151260000800220300001200228490000700240520121800247653002701465653003901492653002401531653001501555653002801570100002101598700003001619856012701649 2022 eng d a0141-549200aBiosynthetic process and strain improvement approaches for industrial penicillin production0 aBiosynthetic process and strain improvement approaches for indus cFEB a179-1920 v443 a

Penicillins and cephalosporins are the most important class of beta (beta) lactam antibiotics, accounting for 65% total antibiotic market. Penicillins are produced by Penicillium rubens (popularly known as P. chrysogenum) were used to synthesize the active pharmaceutical intermediate (API), 6-aminopenicillinic acid (6-APA) employed in semisynthetic antibiotic production. The wild strains produce a negligible amount of penicillin (Pen). High antibiotic titre-producing P. chrysogenum strains are necessitating for industrial Pen production to meet global demand at lower prices. Classical strain improvement (CSI) approaches such as random mutagenesis, medium engineering, and fermentation are the cornerstones for high-titer Pen production. Since, Sir Alexander Fleming Discovery of Pen, great efforts are expanded to develop at a commercial scale antibiotics producing strains. Breakthroughs in genetic engineering, heterologous expression and CRISPR/Cas9 genome editing tools opened a new window for Pen production at a commercial scale to assure health crisis. The current state of knowledge, limitations of CSI and genetic engineering approaches to Pen production are discussed in this review.

10abeta-lactam antibiotic10aClassical strain improvement (CSI)10aGenetic engineering10aPenicillin10aPenicillium chrysogenum1 aSawant, Amol, M.1 aVamkudoth, Koteswara, Rao uhttps://library.ncl.res.in/content/biosynthetic-process-and-strain-improvement-approaches-industrial-penicillin-production02633nas a2200217 4500008004100000245015900041210006900200260000800269300001500277490000600292520177700298653002302075653003902098653002302137653001702160653002302177653003302200100002902233700003002262856012302292 2025 eng d00aComprehensive investigation on statistical approaches and classical strain improvement for penicillin V production by Penicillium rubens BIONCL P45 strain0 aComprehensive investigation on statistical approaches and classi cJAN a1302 -13270 v53 a

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.

10aBox-Behnken design10aClassical strain improvement (CSI)10aMedia optimization10aPenicillin V10aPenicillium rubens10aResponse surface methodology1 aSawant, Amol, Muralidhar1 aVamkudoth, Koteswara, Rao uhttps://library.ncl.res.in/content/comprehensive-investigation-statistical-approaches-and-classical-strain-improvement