Sustainable and tunable polyhydroxybutyrate-co-hydroxyvalerate and polyhydroxybutyrate-co-hydroxyhexanoate production by Cupriavidus necator from molasses with potential use in biomedical applications

The high production cost of polyhydroxyalkanoates (PHAs) remains a major limitation for their large-scale implementation, motivating the development of sustainable and low-cost bioprocesses based on industrial waste valorization. The main objective of the present study was to improve fermentation conditions for sustainable and tunable production of polyhydroxybutyrate-co-hydroxyvalerate (PHBV) and polyhydroxybutyrate-co-hydroxyhexanoate (PHBHHx) from industrial waste by wild-type Cupriavidus necator with potential use in biomedical applications. Untreated molasses, a byproduct of the sugar industry, were selected as the main carbon source after evaluating several industrial wastes. Fermentation strategies were optimized to enhance PHBV and PHBHHx production and fed-batch strategies were implemented using propionic acid or hexanoic acid as co-substrates to promote 3 HV or 3HHx incorporation, respectively. The 3 HV mole fraction in PHBV was adjusted from 1 to 25.7 mol%, while the 3HHx mole fraction in PHBHHx was tuned from 1 to 7.4 mol%. The resulting copolymers were processed into three-dimensional scaffolds, which supported fibroblast growth and viability, indicating their suitability for preliminary biomedical evaluation. Overall, this study demonstrates that untreated molasses is an effective low-cost source for the sustainable production of tunable PHBV and PHBHHx using the model bacterium C. necator, establishing a promising platform for the development of PHA-based scaffolds for biomedical applications, particularly for tissue regeneration.