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Hyaluronic acid production is enhanced by the additional co-expression of UDP-glucose pyrophosphorylase in Lactococcus lactis

  • Applied Genetics and Molecular Biotechnology
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Abstract

Hyaluronic acid (HA) production was metabolically engineered in Lactococcus lactis by introducing the HA synthetic machinery from the has operon of the pathogenic bacterium Streptococcus zooepidemicus. This study shows that the insertion of uridine diphosphate (UDP)-glucose pyrophosphorylase (hasC) gene in addition to the HA synthase (hasA) and UDP-glucose dehydrogenase (hasB) genes has a significant impact on increasing HA production. The recombinant L. lactis NZ9000 strain transformed with the plasmid pSJR2 (co-expressing hasA and hasB genes only) produced a maximum of 107 mg/l HA in static flask experiments with varying initial glucose concentrations, while the corresponding experiments with the transformant SJR3 (co-expressing hasA, hasB, and hasC genes) gave a maximum yield of 234 mg/l HA. The plasmid cloned with the insertion of the full has operon comprising of five different genes (hasA, hasB, hasC, hasD, and hasE) exhibited structural instability. The HA yield was further enhanced in batch bioreactor experiments with controlled pH and aeration, and a maximum of 1.8 g/l HA was produced by the SJR3 culture.

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Acknowledgments

The authors would like to acknowledge the financial support provided by Indian Institute of Technology Madras for this project and Dr. Kalpana Sriraman for her valuable comments and suggestions toward this work.

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Authors and Affiliations

  1. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India

    Shashi Bala Prasad, Guhan Jayaraman & K. B. Ramachandran

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  1. Shashi Bala Prasad
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  2. Guhan Jayaraman
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  3. K. B. Ramachandran
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Correspondence to K. B. Ramachandran.

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Prasad, S.B., Jayaraman, G. & Ramachandran, K.B. Hyaluronic acid production is enhanced by the additional co-expression of UDP-glucose pyrophosphorylase in Lactococcus lactis . Appl Microbiol Biotechnol 86, 273–283 (2010). https://doi.org/10.1007/s00253-009-2293-0

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