Engineering the Methyltransferase Through Inactivation of the Genk and Genl Leads to a Significant Increase of Gentamicin C1a Production in an Industrial Strain of Micromonospora Echinospora 49-92S
Bioprocess and biosystems engineering(2022)
摘要
In this study, a single-component high-yielding Micromonospora echinospora strain 49-92S-KL01 was constructed by deleting methyltransferase-encoding genes genK and genL. In 5-L fermentation trials, gentamicin C1a titers in the mutant strain were 3.22-fold higher than that in the parental strain (211 U/mL vs. 50 U/mL). The glycolysis pathway and tricarboxylic acid cycle fluxes were reduced by 26.8% and 26.6%, respectively, compared to the parental strain according to the metabolic flux analysis during the stationary phase, resulting in lower levels of energy supplements required for the cellular maintenance. Meanwhile, a significant enhancement in precursor (paromamine) accumulation and availability was observed in 49-92S-KL01 compared to parental strain. These results indicate that genK and genL significantly affect the synthesis of gentamicin C1a. In addition, this study provides a more rational strategy for gentamicin C1a production.
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关键词
Micromonospora echinospora,Gentamicin C1a,Methyltransferase,GenK–genL,Metabolic flux analysis
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