"Metabolic engineering of microbial hosts for the biosynthesis of high molecular weight hyaluronan"

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Recent advancements in recombinant bacteria for hyaluronan (HA) production highlight significant advantages over traditional extraction methods from animal tissues or pathogenic bacteria, including reduced organic solvent use, non-toxic host organisms, and minimal downstream processing. However, these systems often produce HA with low molecular weight (MW), which is a critical limitation. This study aims to develop a recombinant microbe capable of producing HA with a MW of 2 MDa or higher. Two primary strategies are employed: 1. Utilizing Saccharomyces cerevisiae, a well-established industrial organism with accessible genetic tools, allows for the investigation of HA synthases from higher eukaryotes, which can be complex to express in prokaryotic hosts. The extensive knowledge of S. cerevisiae physiology aids in genome manipulation by deleting unwanted pathways and integrating new genes, while a synthetic pathway for precursor supply enhances HA synthesis. 2. Exploring various Streptococcus species known for producing HA of differing MWs, this study examines whether sequence variations in streptococcal synthases correlate with MW differences. Additionally, two new HA synthases from Streptococcus parauberis and Streptococcus iniae are analyzed. The behavior of these synthases under HA production conditions in recombinant Lactococcus lactis is also investigated to assess performance variations in vitro.