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<p>Hyaluronic acid (HA), a linear high-polymerization polysaccharide composed of repeating D-glucuronic acid and N-acetylglucosamine units, has gained significant attention due to its notable viscoelastic properties, high moisture retention capacity, and excellent biocompatibility. These unique characteristics have enabled its widespread applications across diverse sectors including biomedical engineering, advanced cosmeceuticals, and functional food industries. Emerging evidence indicates that the functional performance of HA is critically dependent on its molecular weight (Mw), with distinct biological roles and application domains being associated with high molecular weight HA (HMW-HA), low molecular weight HA (LMW-HA), and HA oligosaccharides (o-HA). Although substantial research efforts in recent years have been devoted to developing Mw regulation strategies for HA, a comprehensive synthesis of these methodologies remains scarce. This review systematically consolidates cutting-edge advancements in HA Mw modulation through four principal approaches: genetic engineering of HA synthases, enzymatic depolymerization techniques, metabolic pathway engineering, and optimization of fermentation parameters. Furthermore, we critically discuss current technological challenges and propose future research directions, establishing a methodological framework for the industrial-scale production of HA with precisely controlled Mw profiles.</p>

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Molecular weight regulation strategies in microbial synthesis of hyaluronic acid: current status and future perspectives

  • 期刊论文

  • 发表日期：

    2025年12月31日

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  • Xiang Ma,
  • Xinyue Fan,
  • Shenglong Wang,
  • Ziyi Zhao,
  • Ziyao Zheng,
  • Jun Li,
  • Xueqian Dong,
  • Hao Liu,
  • Weixia Gao

摘要

Hyaluronic acid (HA), a linear high-polymerization polysaccharide composed of repeating D-glucuronic acid and N-acetylglucosamine units, has gained significant attention due to its notable viscoelastic properties, high moisture retention capacity, and excellent biocompatibility. These unique characteristics have enabled its widespread applications across diverse sectors including biomedical engineering, advanced cosmeceuticals, and functional food industries. Emerging evidence indicates that the functional performance of HA is critically dependent on its molecular weight (Mw), with distinct biological roles and application domains being associated with high molecular weight HA (HMW-HA), low molecular weight HA (LMW-HA), and HA oligosaccharides (o-HA). Although substantial research efforts in recent years have been devoted to developing Mw regulation strategies for HA, a comprehensive synthesis of these methodologies remains scarce. This review systematically consolidates cutting-edge advancements in HA Mw modulation through four principal approaches: genetic engineering of HA synthases, enzymatic depolymerization techniques, metabolic pathway engineering, and optimization of fermentation parameters. Furthermore, we critically discuss current technological challenges and propose future research directions, establishing a methodological framework for the industrial-scale production of HA with precisely controlled Mw profiles.