Reifenberg Philipp, Rosenberger Lara, Mignon Maxime Le, Zimmer Aline
Merck Life Science KGaA, Upstream R&D, Darmstadt, Germany.
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
Biotechnol J. 2025 Jun;20(6):e70041. doi: 10.1002/biot.70041.
Keto isoleucine and keto leucine are bioavailable amino acid precursors in CHO cells producing biotherapeutics. Following their supplementation in a fed-batch culture with CHOK1 GS cells, quantitation of metabolites derived from the three branched-chain keto acids revealed a decrease of their decarboxylation products, but an accumulation of their α-hydroxy acids. The latter had minor effects on cell growth and productivity. L-lactate dehydrogenase was identified as the key enzyme forming valine's α-hydroxy acid.
酮异亮氨酸和酮亮氨酸是用于生产生物治疗药物的中国仓鼠卵巢(CHO)细胞中具有生物利用度的氨基酸前体。在用CHOK1 GS细胞进行的补料分批培养中添加它们之后,对源自三种支链酮酸的代谢物进行定量分析发现,它们的脱羧产物减少,但α-羟基酸积累。后者对细胞生长和生产力的影响较小。L-乳酸脱氢酶被确定为形成缬氨酸α-羟基酸的关键酶。