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Taehee HAN,Gi Bae KIM,Cheon Woo MOON,Sang Yup LEE 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
There has been increasing industrial demand for five-carbon platform chemicals, particularly glutaric acid, a widely used building block for the synthesis of polyesters and polyamides. Here, we report the development of an efficient glutaric acid microbial producer by systems metabolic engineering of an L-lysine-overproducing Corynebacterium glutamicum BE strain. Based on our previous study, an optimal synthetic metabolic pathway comprising Pseudomonas putida L-lysing monooxygenase (davB) and 5-aminovaleramide amidohydrolase (davA) genes and C. glutamicum 4-aminobutyrate aminotransferase (gabT) and succinate-semialdehyde dehydrogenase (gabD) genes was introduced into the C. glutamicum BE strain. Through system-wide analyses, including genome-scale metabolic simulation, comparative transcriptome analysis, and flux response analysis, 11 target genes to be engineered were identified and expressed at desired levels to increase the supply of direct precursor L-lysine and reduce precursor loss. A glutaric acid exporter encoded by ynfM was newly discovered and over-expressed to further improve glutaric acid production. Fermentation conditions including oxygen transfer rate, batch-phase glucose level, and nutrient feeding strategy, were optimized for the efficient production of glutaric acid. In fed-batch culture, the final engineered strain produced 105.3 g/L of glutaric acid in 69h without any byproduct. The systems metabolic engineering and fermentation optimization strategies described here will be useful for developing engineered microbial hosts for the efficient bio-based production of other chemicals of interest to industry.
한태희(Taehee Han) 한국의학교육학회 2015 Korean journal of medical education Vol.27 No.3
Reductive logic has been a major reasoning style in development of modern biomedical sciences. However, when “medical humanities” is developed by reductive reasoning, integrative and holistic values of humanities tend to be weakened. In that sense, identity and significance of “medical humanities” continue to be controversial despite of its literal clarity. Humanities in medical education should be established by strengthening humanistic and socialistic aspects of regular medical curriculum as well as developing individual “medical humanities” programs.