A Review of Metabolic Pathways and Genetic Engineering Strategies for Enhanced Polyhydroxybutyrate Production

The production of biodegradable plastics is considered one of the best alternatives to combat plastic waste and global pollution. Polyhydroxybutyrate (PHB) stands out as the most studied bioplastic, but its introduction into global industries and markets still presents challenges due to the high final cost. Understanding the entire synthesis process of this biopolymer becomes a more effective way to address this problem. This review describes the four main natural metabolic pathways related to PHB biosynthesis, associated with stages involving sugars, fatty acid metabolism, de novo fatty acid synthesis, and the butyric acid pathway, while also addressing the role of acetyl-CoA as the central precursor molecule. Approaches regarding physicochemical conditions and the selection of ideal substrates were also conducted, aiming at the production of PHB that is both economically viable and environmentally sustainable. Thus, this review distinguishes itself by bringing an updated and comprehensive overview of PHB biosynthesis, whereas other reviews tend to address specific aspects of PHA production. Furthermore, some knowledge gaps were identified, and different genetic engineering strategies were discussed, such as gene overexpression, deletion of competitive pathways, application of the CRISPRi technique, and two-stage fermentation, which have shown promise in optimizing PHB synthesis and reducing production costs.