L-lysine production improvement: a review of the state of the art and patent landscape focusing on strain development and fermentation technologies

Abstract

L-lysine is an essential amino acid used in various industrial sectors but mainly in food and animal feed. Intense research has been directed toward increasing its productivity. This literature review presents the state of the art and patent landscape of the industrial production of L-lysine, with a focus on the strain development and fermentation technologies, through geographic, social, and chronological analysis, using the text mining technique. The geographic analysis showed a greater tendency for countries with industrial plants with large production capacity to submit patents or publish articles, while the social analysis reflected the close relationship between educational units and companies. The technologies of each document were divided into optimization of fermentation parameters, conventional mutation, and genetic engineering. Corynebacterium glutamicum and Escherichia coli present the most attractive industrial phenotypes, and their cultivation occurs mainly in fed-batch processes with control parameters carefully selected to enhance metabolism. These strains are generally modified by conventional approaches (e.g., mutagenesis and selection of auxotrophic and/or regulatory mutants) or by genetic engineering technologies. The combination of both these approaches enables genomic breeding and the construction of strains with industrial potential, capable of accumulating more than 120 g/L of L-lysine. From the analysis of these approaches, we developed a descriptive flow of substrate uptake, amino acid metabolism, and mechanisms of excretion of a lysine-producing model cell. It is expected that the various mechanisms of L-lysine production, here shown and described, will become a guide that aids in increasing amino acid productivity without interfering with the strain stability.