Lysine Fermentation: History and Genome Breeding

Abstract

Lysine fermentation by Corynebacterium glutamicum was developed in 1958 by Kyowa Hakko Kogyo Co. Ltd. (current Kyowa Hakko Bio Co. Ltd.) and is the second oldest amino acid fermentation process after glutamate fermentation. The fundamental mechanism of lysine production, discovered in the early stages of the process's history, gave birth to the concept known as "metabolic regulatory fermentation," which is now widely applied to metabolite production. After the development of rational metabolic engineering, research on lysine production first highlighted the need for engineering of the central metabolism from the viewpoints of precursor supply and NADPH regeneration. Furthermore, the existence of active export systems for amino acids was first demonstrated for lysine in C. glutamicum, and this discovery has resulted in the current recognition of such exporters as an important consideration in metabolite production. Lysine fermentation is also notable as the first process to which genomics was successfully applied to improve amino acid production. The first global "genome breeding" strategy was developed using a lysine producer as a model; this has since led to new lysine producers that are more efficient than classical industrial producers. These advances in strain development technology, combined with recent systems-level approaches, have almost achieved the optimization of entire cellular systems as cell factories for lysine production. In parallel, the continuous improvement of the process has resulted not only in fermentation processes with reduced load on downstream processing but also in commercialization of various product forms according to their intended uses. Nowadays lysine fermentation underpins a giant lysine demand of more than 2 million metric tons per year.

Sustainable Production of N-methylphenylalanine by Reductive Methylamination of Phenylpyruvate Using Engineered Corynebacterium glutamicum

“…Upon repeated addition of the substrates in a scale-up experiment the yield was dramatically reduced, which was attributed to inactivation of glucose dehydrogenase [52]. By contrast, although not studied here, the scale-up of fermentative C. glutamicum processes typically benefits from the experience of 60 years of amino acid production at the million-ton scale using this bacterium [53,54].…”

Amino Acid δ15N Can Detect Diet Effects on Pollution Risks for Yellow-Legged Gulls Overlooked by Trophic Position

“…Lysine is an essential amino acid in the diet of animals and is one of the major additives to feed stocks, notably for poultry and swine raising (Toride, 2002). It is produced industrially through fermentation with the addition of sugars and inorganic nitrogen (Ikeda, 2017). Industrial lysine is likely to have low δ 15 N, since ammonium derived from atmospheric nitrogen represents the most economic source for fertilizers (Smil, 2001).…”

Carotenoid Production by Corynebacterium: The Workhorse of Industrial Amino Acid Production as Host for Production of a Broad Spectrum of C40 and C50 Carotenoids

“…Since its discovery as a natural glutamate producer in the 1950s [4], its production spectrum was broadened. Lysine is the second biggest production volume being generated by this microbe [5,6]. Sequencing of its genome [7], the development of a well-filled genetic toolbox [8] and establishment of large-scale fermentations [9] boosted investigations of a wide set of industrially relevant compounds.…”