Replacement of Isoleucine and Leucine by their Keto Acids leads to increased formation of α‐Hydroxy Acids in Chinese Hamster Ovary cells

ABSTRACT 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.