Substrate inhibition versus product feedback inhibition: In the perspective of single molecule enzyme kinetics

Abstract

In this work, we study the origin of dynamic disorder in a simple reaction network of substrate inhibition and product feedback inhibition loop. It is well established that dynamic disorder arises in a biochemical reaction network not only due to enzymatic fluctuations influencing the catalytic rate but also due to the physical presence of inhibitors owing to their transition between active and inhibited states of enzymes. But we show here, for networks, where there is explicitly no physical presence of an inhibitor but either the reactant or the product in time course of the reaction possesses to be the one. There is a strikingly noticeable dependence of the randomness parameter on the substrate concentration that can discriminate between both the phenomena under consideration.

Rational Design of a De Novo Enzyme Cascade for Scalable Continuous Production of Antidepressant Prodrugs

“…12,13 The other challenge is that applying CFB to industries cannot be implemented directly, as they are susceptible to the inhibition of substrates 14,15 or products 16,17 at elevated concentrations, which means that the velocity curve of the reaction rises to a maximum as the substrate or product concentration increases and then descends either to zero (complete inhibition) or a nonzero asymptote (partial inhibition) due to the predefined active site geometry of enzymes and the similarity of substrates and products. 18 Therefore, the integration and even cooperation of CFB systems and immobilization biotechnology have a tendency to improve the stability of enzymes and enable the recycling of biocatalysts to maximize the catalytic efficiency for the continuous accumulation of products. 19 The current enzyme immobilization techniques mainly exploit covalent bonds 20 and noncovalent bonds 21 to immobilize enzymes.…”

“…Compared to the metabolic engineering method, CFB is a promising approach with advantages of facile plug-and-play cascade assembly, flexible reaction conditions, and direct access to the reaction environment for monitoring, manipulation, and maintenance. , Although CFB systems have been driving biological processes in an efficient and adaptable manner, their industrial applications still face two main challenges. One is that most important enzymes are delicate and struggle to achieve continuous catalysis as well as long-term use. , The other challenge is that applying CFB to industries cannot be implemented directly, as they are susceptible to the inhibition of substrates , or products , at elevated concentrations, which means that the velocity curve of the reaction rises to a maximum as the substrate or product concentration increases and then descends either to zero (complete inhibition) or a nonzero asymptote (partial inhibition) due to the predefined active site geometry of enzymes and the similarity of substrates and products . Therefore, the integration and even cooperation of CFB systems and immobilization biotechnology have a tendency to improve the stability of enzymes and enable the recycling of biocatalysts to maximize the catalytic efficiency for the continuous accumulation of products …”