Japanese researchers develop tech to improve biosynthetic production

In Japan, biosynthetic production, controlling engineered bacteria to efficiently produce chemicals is challenging due to mismatches between process models and actual outcomes. To address this issue, researchers from Japan developed a hybrid control system that combines a computer-based model controller with a feedback mechanism engineered directly into Escherichia coli bacteria. Simulation results show that this hybrid control approach achieved higher yields than other methods, highlighting its potential to improve industrial bioprocesses efficiency and reduce environmental impact.

Control systems are ubiquitous in modern day technology. In industrial contexts, these systems ensure that relevant variables remain within a desirable range to keep processes running safely and efficiently. A vast array of control strategies exists, and it is not uncommon to combine different types of controllers to improve performance. For instance, high-level controllers based on mathematical modeling of a given process are routinely combined with low-level controllers, such as the widely used Proportional–Integral–Derivative (PID) controller, which does not rely on models and instead uses real-time feedback to adjust control actions.

Combining different controllers is not, however, a straightforward endeavor. In biosynthesis plants, where engineered bacteria are used to produce desired products, the concentrations of specific substances inside the microorganisms represent important control variables. Not only are these variables difficult to measure accurately but control systems must also address inaccuracies between the mathematical models used and the actual process. Addressing these process-model mismatches (PMMs) is a significant challenge in controlling biosynthetic processes.

Fortunately, a research team led by the Graduate School of Science and Technology at Nara Institute of Science and Technology and Fujita Health University, Japan, has been actively investigating a promising solution to this problem. In their latest study published in volume 14 of Scientific Reports on November 18, 2024, they present a convincing proof-of-concept for a hybrid ‘in silico/in-cell’ controller (HISICC). The team’s technology combines a computer-driven, model-based optimization controller with a feedback control mechanism engineered directly into an Escherichia coli (E. coli) bacteria strain engineered for producing fatty acids.