Heparosan is a linear polysaccharide comprised of repetitive disaccharide units of α-1,4-N-acetylglucosamine and β-1,4-glucuronic acid. It is primarily used as a precursor molecule for the chemoenzymatic synthesis of heparosan. Based on the molecular weight, heparosan finds applications in biomaterials and drug delivery therapeutics. Escherichia coli K5 and Pasteurella multocida type D produce heparosan as a capsular polysaccharide on the cell surface. Heparosan is traditionally produced from E. coli K5 fermentation. Recently, metabolic engineering and synthetic biology approaches enabled the production of heparosan in recombinant microbial systems to alleviate the pathogenicity and potential toxins. This chapter summarizes the current state and challenges associated with microbial heparosan production in E. coli K5 and other recombinant systems.