A Computational Metabolic Model for Engineered Production of Resveratrol in Escherichia coli

Abstract

Although engineered microbial production of natural compounds provides a promising alternative method to plant production and extraction, the process can be inefficient and ineffective in terms of time and cost. To render microbial systems profitable and viable, the process must be optimized to produce as much product as possible. To this end, this work illustrates the construction of a new probabilistic computational model to simulate the microbial production of a well-known cardioprotective molecule, resveratrol, and the implementation of the model to enhance the yield of the product in Escherichia coli. This model identified stilbene synthase as the limiting enzyme and informed the effects on changes in concentration and source of this enzyme. These parameters, when employed in a laboratory system, were able to improve the titer from 62.472 mg/L to 172.799 mg/L, demonstrating the model's ability to produce a useful simulation of a dynamic microbial resveratrol production system.

Efficient biosynthesis of pinosylvin from lignin-derived cinnamic acid by metabolic engineering of Escherichia coli

“…Currently, many STSs have been characterized from plants, and most of them have been applied in the formation of resveratrol [ 27 , 28 ]. However, only AhSTS (STS from Arachis hypogaea ), VvSTS (STS from Vitis vinifera ) and PsSTS (STS from Pinus strobus ) were successfully expressed in E. coli for pinosylvin production [ 12 , 24 , 29 , 30 ]. Pinosylvin is a stilbene that can be predominantly found in the heartwood of coniferous trees of the genus Pinus .…”

Synthetic Biology-Driven Microbial Production of Resveratrol: Advances and Perspectives

“…Additionally, E. coli is more suitable for resveratrol production than yeast because of its high tolerance to p-coumaric acid, another advantage (Shin et al, 2011;Huang et al, 2013) (Donnez et al, 2009). Recently, Zhang et al identified stilbene synthase as the limiting enzyme via a novel probabilistic computational model and improved the final resveratrol titer from 62.472 mg/L to 172.799 mg/L, proving the model useful for predicting and improving biological production (Cotner et al, 2021). Engineered C. glutamicum has also been employed as a vehicle for resveratrol production.…”

Breaking the Bottleneck in Anticancer Drug Development: Efficient Utilization of Synthetic Biology

“…In a computational metabolic model, researchers can obtain a simulation that resembles a real laboratory experiment and an approximate outcome of the experiment by running a model in which researchers can adjust the parameters of every factor in the biosynthetic pathway to optimize the output of the end product ( Figure 4 C). For example, Michael C et al achieved a three-fold improvement in the resveratrol titer in Escherichia coli ( E. coli ) by constructing a new probabilistic computational model [ 166 ]. In addition to metabolic modeling, computational models are also used to design cell factories to realize the optimal production of target molecules [ 167 ].…”