Optimizing the Production of Valuable Metabolites using a Hybrid of Constraint-based Model and Machine Learning Algorithms: A Review

The advances in genome sequencing and metabolic engineering have allowed the reengineering of the cellular function of an organism. Furthermore, given the abundance of omics data, data collection has increased considerably, thus shifting the perspective of molecular biology. Therefore, researchers have recently used artificial intelligence and machine learning tools to simulate and improve the reconstruction and analysis by identifying meaningful features from the large multi-omics dataset. This review paper summarizes research on the hybrid of constraint-based models and machine learning algorithms in optimizing valuable metabolites. The research articles published between 2020 and 2023 on machine learning and constraint-based modeling have been collected, synthesized, and analyzed. The articles are obtained from the Web of Science and Scopus databases using the keywords: "Machine learning", "flux balance analysis", and "metabolic engineering". At the end of the search, this review contained 13 records. This review paper aims to provide current trends and approaches in in silico metabolic engineering while providing research directions by highlighting the research gaps. In addition, we have discussed the methodology for integrating machine learning and constraint-based modeling approaches.