ArticleFrontiers in microbiology2026
A universal medium bridging the shake-flask to fermenter gap in
Article in Frontiers in microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Zearalenone (ZEN) lactonase is a commercially promising enzyme that catalyzes the conversion of zearalenone into less toxic metabolites and has been expressed in Methods: Using a data-driven approach combined with rational analysis, an optimized medium (FM4CSP) was developed for both systems. Results: ZEN lactonase activity reached 25.87 ± 0.52 U/mL in shake flasks with FM4CSP medium, whereas it was negligible in the conventional FM22 medium. To elucidate the underlying mechanisms, comparative transcriptomic and nitrogen composition analyses were conducted. The results revealed that organic nitrogen sources enhance heterologous protein expression by alleviating energy metabolic stress under oxygen-limited conditions. Large peptides serve as core active components, acting as slow-release nitrogen sources that maintain stable amino acid availability. The balanced peptide profile in complex nitrogen sources triggered metabolic reprogramming, including downregulation of reducing equivalent-generating pathways to prevent NADH accumulation and upregulation of oxidative phosphorylation to match energy supply with oxygen availability. The effectiveness of FM4CSP was further validated in a 30 L fermenter, where ZEN lactonase activity reached 327.56 ± 1.78 U/mL, representing a 1.59-fold increase compared with the conventional FM22 medium. Conclusion: This study developed a novel universal medium (FM4CSP) for both shake-flask and fermenter systems using a cost-effective corn steep powder (CSP) as a slow-release nitrogen source. This medium effectively bridges the compatibility gap between both systems and provides a scalable strategy for heterologous protein production in
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