Directed Evolution of Hyaluronic Acid Synthase

  Hyaluronic Acid Copyright: © Bio VI This figure demonstrates the improved flexibility of the N-terminal of pmHAS with the triple substitution (T40L, V59M and T104A). The final variant, pmHAS-VF, can produce HA up to 4.7 MDa with a 2-fold improvement in mass-based turnover number.

In John´s new publication, engineered hyaluronan synthase from Pasteurella multocida pmHAS-VF harbouring triple substitutions, T40L, V59M and T104A, exhibited improved N-terminal region flexibility and enhanced hyaluronic acid polymerizing activity. Production of high molecular weight hyaluronic acid up to 4.7 MDa at twice the normal output can now be achieved. Hyaluronic acid is the natural glycosaminoglycan product with diverse cosmetic and medical applications and a global market value of $8.3 billion. This protein engineering campaign not only demonstrates the applicability of protein engineering towards improved hyaluronic acid production, but also uncovers the potential involvement of the N-terminus in hyaluronic acid synthesis. This work was realized in the division Biohybrid System and it was possible through DBU funding.

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