Overview of Enzyme Engineering Towards the Production of Hyaluronic Acid with Tailored Molecular Weight
: Hyaluronic acid or hyaluronan (HA) is a natural biopolymer composed of D-glucuronic acid and N-acetylglucosamine units, distributed as a non-sulfated and anionic glycosaminoglycan in important tissues of the body, and is commercially and biologically important. Its biological properties are determined by the molecular weight and dispersity which are suitable for particular medical and cosmetic applications. The synthesis of well-defined and monodisperse HA is still a significant obstacle and an impressive research field for advanced medical applications. High polydispersity by bacterial fermentation, the lack of knowledge of the mechanism required to start and continue the synthesis process, increased cost of raw materials to produce HA, clarification and explanation of factors limiting synthesis in bacterial systems are among the important challenges of hyaluronic acid synthesis. Hyaluronan synthase plays a critical role in HA molecular mass by producing a wide range of HA involved in various biological processes. Hyaluronan biosynthesis has been considered extensively; however, the control of its size and weight during the synthesis process is poorly investigated. This review focuses on these uncharted biochemical details to obtain the uniform chain lengths of Hyaluronan by protein engineering and regulating the function of Hyaluronan synthase.