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. The technologies developed in the L-lysine field are registered in documents such as patents and articles, which can be used to trace the technical-scientific and sociogeographical production profile. To study these profiles, a text-mining technique associated with carefully formulated keywords was used. Geographic analysis has shown 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. Some of these companies presented a direction of effort for their physical or theoretical capacity expansion at different time intervals. The chronological analysis allows us to highlight the role of articles and patents in the registration of the technological transition. The technologies of each document were divided into (1) optimization of fermentation parameters, (2) conventional mutation, and (3) genetic engineering. Finally, the documents of the first technological class were evaluated and discussed, emphasizing the great interest in conducting continuous and fed batch processes and in the fermentative parameter controls that lead to cell metabolism in order to favor L-lysine formation. Furthermore, a descriptive flow of the substrate uptake mechanism and an amino acid metabolism and excretion mechanism were developed for the illustration of microbial physiology and molecular technologies to increase L-lysine productivity.

Improving lysine production through construction of an Escherichia coli enzyme‐constrained model

“…The ec_ i ML1515 model can thus assist in clarifying intracellular mechanisms such as the change in protein synthesis in E. coli following culture on different nitrogen sources and DO levels. After performing such changes under the guidance of the ec_ i ML1515 model, the lysine titer increased to a level comparable with the highest ever reported (Felix et al, 2019). In summary, the ec_ i ML1515 model is a powerful tool that can be used to accurately predict and rationally design cellular phenotypes.…”

Reconstruction of the Diaminopimelic Acid Pathway to Promote L-lysine Production in Corynebacterium glutamicum

“…L-lysine is an essential amino acid widely used in food, animal feed, medicine, cosmetics, and other industries [1]. Methods to produce L-lysine include albuminolysis, chemical method, enzymic method, and microbial fermentation.…”

“…Microbial fermentation uses renewable feedstock and produces low amounts of pollutants [2]. Therefore, L-lysine is mainly produced by microbial fermentation in the industries, with C. glutamicum and Escherichia coli being the most commonly used strains [1].…”

A Non-linear Model Predictive Control Based on Grey-Wolf Optimization Using Least-Square Support Vector Machine for Product Concentration Control in l-Lysine Fermentation

“…One of the best ways to boost the productivity is to monitor and control product concentration. An excessive increase of product in reactor causes osmotic stress or catabolic repression for bacteria during cultivation [ 8 ]. Temperature, pH, initial substrate concentration, air flow rate and agitation rate are five paramount factors to enhance and control product concentration [ 9 ].…”