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

Abstract Heparosan, a natural polymer with unique chemical and biological properties, holds great promise for various biomedical applications. Of particular interest is the production of low molecular weight and low polydisperse heparosan polymers, which offer enhanced functionality and suitability for therapeutic and diagnostic purposes. Polydispersity, a measure of the distribution of molecular weight within a polymer sample, is a critical factor influencing the performance of heparosan-based materials. Achieving precise control over the synthesis process to consistently produce heparosan with low molecular weight and low polydispersity index can be challenging, requiring tight regulation of reaction conditions, enzyme activity, and precursor concentrations. To address this challenge, we propose a novel approach utilizing synthetic biology principles to precisely control heparosan biosynthesis in Escherichia coli (E. coli). Our strategy involves the design and implementation of a biomolecular controller capable of regulating the expression of genes involved in heparosan biosynthesis using biosensors of both precursors, thereby enabling fine-tuned control over the polymerization process. Through this approach, we successfully envision the implementation of the proposed system, demonstrating the potential to produce heparosan in probiotic E. coli Nissle 1917 with a low Mw and a low PDI that meets the stringent quality standards required for biomedical applications. This study represents a significant advancement in the field of heparosan production, offering new opportunities for the development of advanced biomaterials with tailored properties for diverse biomedical applications.