2-Ketoisocaproate synthesis in Corynebacterium glutamicum and role of the key enzyme isopropylmalate synthase

Abstract

The natural precursor of the essential amino acid L-leucine, 2-ketoisocaproate, is often used as a therapeutic agent in infusion solutions for kidney-patients and as integral part of functional food for muscle regeneration. Moreover, 2-ketoisocaproate may serve as precursor for products deriving from this 2-ketoacid, e.g. 3-methylbutanal (isovaleraldehyde), an intermediate for industrial vitamin synthesis, as well as its corresponding alcohol 3-methyl-1-butanol, a potential future biofuel. In the present work, the efficient, growth-coupled production of 2-ketoisocaproate with metabolically engineered Corynebacterium glutamicum strains was pursued. In this context, potential limitations during 2-ketoisocaproate synthesis in C. glutamicum were identified, permitting the directed improvement of the newly constructed strain(s).