Artificial Intelligence (AI) technology is spearheading a new industrial revolution, which provides ample opportunities for the transformational development of traditional fermentation processes. During plasmid fermentation, traditional subjective process control leads to highly unstable plasmid yields. In this study, a multi-parameter correlation analysis was first performed to discover a dynamic metabolic balance among the oxygen uptake rate, temperature, and plasmid yield, whilst revealing the heating rate and timing as the most important optimization factor for balanced cell growth and plasmid production. Then, based on the acquired on-line parameters as well as outputs of kinetic models constructed for describing process dynamics of biomass concentration, plasmid yield, and substrate concentration, a machine learning (ML) model with Random Forest (RF) as the best machine learning algorithm was established to predict the optimal heating strategy. Finally, the highest plasmid yield and specific productivity of 1167.74 mg L

A machine learning‐based approach for improving plasmid DNA production in Escherichia coli fed‐batch fermentations