Heterologous Production of Hyaluronic Acid in an ε-Poly-L-Lysine Producer, Streptomyces albulus

Applied and Environmental Microbiology
Tomohiro YoshimuraKazuya Yamanaka

Abstract

Hyaluronic acid (HA) is used in a wide range of medical applications, where its performance and therapeutic efficacy are highly dependent on its molecular weight. In the microbial production of HA, it has been suggested that a high level of intracellular ATP enhances the productivity and molecular weight of HA. Here, we report on heterologous HA production in an ε-poly-l-lysine producer, Streptomyces albulus, which has the potential to generate ATP at high level. The hasA gene from Streptococcus zooepidemicus, which encodes HA synthase, was refactored and expressed under the control of a late-log growth phase-operating promoter. The expression of the refactored hasA gene, along with genes coding for UDP-glucose dehydrogenase, UDP-N-acetylglucosamine pyrophosphorylase, and UDP-glucose pyrophosphorylase, which are involved in HA precursor sugar biosynthesis, resulted in efficient production of HA in the 2.0 MDa range, which is greater than typical bacterial HA, demonstrating that a sufficient amount of ATP was provided to support the biosynthesis of the precursor sugars, which in turn promoted HA production. In addition, unlike in the case of streptococcal HA, S. albulus-derived HA was not cell associated. Based on these findings...Continue Reading

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Citations

Jul 3, 2016·Microbial Cell Factories·Juliana Davies de OliveiraNádia Skorupa Parachin
Dec 31, 2015·Current Opinion in Biotechnology·Jian WangYajun Yan
Sep 25, 2017·Biotechnology and Bioengineering·Adam W WestbrookC Perry Chou
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