Synthetic biology design principles enable efficient bioproduction of Heparosan with low molecular weight and low polydispersion index for the biomedical industry

Abstract Heparosan is a natural polymer with unique chemical and biological properties, that holds great promise for biomedical applications. The molecular weight (Mw) and polydispersion index (PDI) are critical factors influencing the performance of heparosan-based materials. Achieving precise control over the synthesis process to consistently produce heparosan with low Mw and low PDI can be challenging, as it requires tight regulation of reaction conditions, enzyme activity, and precursor concentrations. We propose a novel approach utilizing synthetic biology principles to precisely control heparosan biosynthesis in bacteria. Our strategy involves designing a biomolecular controller that can regulate the expression of genes involved in heparosan biosynthesis. This controller is activated by biosensors that detect heparosan precursors, allowing for fine-tuned control of the polymerization process. Through this approach, we foresee the implementation of this synthetic device, demonstrating the potential to produce low Mw and low PDI heparosan in the probiotic E. coli Nissle 1917 as a biosafe and biosecure biofactory. This study represents a significant advancement in the field of heparosan production, offering new opportunities for the development and manufacturing of biomaterials with tailored properties for diverse biomedical applications.