Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems

L-asparaginase is one of the world’s most in-demand industrial enzymes, mainly due to its therapeutic properties and its use in the food industry. Over the years studies have been conducted to improve its specific activity and reduce side effects, driving new discoveries that promise safer, more efficient, and cheaper drugs for consumers. However, heterologous protein modifications or expression continue to be a problem during production. Therefore, addressing bottlenecks when attempting to express modified and/or heterologous proteins using the rational design of heterologous expression systems with modified hosts could be a promising strategy to improve L-asparaginase production. Problems such as inadequate protein folding, metabolic load on host cells, codon usage bias, repetitive sequences affecting translation, heavy molecular weight and/or multi-membrane domains formation; need great attention during the development of “bio-better” proteins. In this article, we address the current molecular and metabolic strategies that have been developed to improve the heterologous expression of L-asparaginase.