Synthetic Biology Journal

   

Research advances in biosynthesis of hyaluronic acid with controllable molecular weights

Sen XIAO1,2,4, Litao HU1,2,4, Zhicheng SHI1,2, Fayin WANG1,2, Siting YU1,2, Guocheng DU2,3, Jian CHEN2,3,4, Zhen KANG1,2,4   

  1. 1.Key Laboratory of Carbohydrate Chemistry and Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi 214122,China
    2.Science Center for Future Foods,Jiangnan University,Wuxi 214122,China
    3.Key Laboratory of Industrial Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi 214122,China
    4.Institute of Future Food Technology,Jiangsu Industrial Technology Research Institute,Yixing 214200,China
  • Received:2024-08-14 Revised:2024-10-24
  • Contact: Zhen KANG

可控分子量透明质酸的生物合成研究进展

肖森1,2,4, 胡立涛1,2,4, 石智诚1,2, 王发银1,2, 余思婷1,2, 堵国成2,3, 陈坚2,3,4, 康振1,2,4   

  1. 1.江南大学生物工程学院,糖化学与生物技术教育部重点实验室,江苏 无锡 214122
    2.江南大学,未来食品科学中心,江苏 无锡 214122
    3.江南大学生物工程学院,工业生物技术教育部重点实验室,江苏 无锡 214122
    4.江苏省产业技术研究院,食品生物技术研究所,江苏 宜兴 214200
  • 通讯作者: 康振
  • 作者简介:肖森(2002—),男,硕士研究生,研究方向为透明质酸的生物合成与酶工程改造。E-mail:6240201118@stu.jiangnan.edu.cn
    康振(1982—),男,博士,教授,博士生导师,研究方向为食品微生物合成生物学与生物制造。E-mail:zkang@jiangnan.edu.cn
  • 基金资助:
    江南大学食品科学与资源国家重点实验室研发项目(5962060204240220);国家自然科学基金(32370066);中央高校基本科研基金(JUSRP622003);无锡市产业创新研究院试点研发项目(XD24006)

Abstract:

Hyaluronic acid (HA), a natural linear acidic polysaccharide composed of disaccharide units of D-glucuronic acid (D-GlcA) and N-acetylglucosamine (N-GlcNAc), is widely used in the cosmetic and medical fields. Different molecular weight HAs exhibit distinct biophysical properties. High molecular weight HA has stronger viscoelasticity and resistance to degradation, while low molecular weight HA demonstrates enhanced biological functions. The industrial production of HA has made significant progress with the shift from traditional animal tissue extraction to microbial fermentation technology. However, the use of the natural HA-producing strain Streptococcus zooepidemicus presents challenges, such as potential pathogenicity and difficulties in molecular modification, which limit the study of HA biosynthesis with varying molecular weights. Recently, the increasing demand for specific molecular weight HA has driven the application of metabolic engineering and synthetic biology techniques in HA biosynthesis and molecular weight regulation. By identifying the key factors involved in HA synthesis and molecular weight regulation, researchers have developed various strategies to optimize HA synthesis and control its molecular weight. This article first analyzes the limiting factors in the synthesis of medium and high molecular weight HA, focusing on the genetic regulation of HA precursor synthesis pathways and the weakening of competitive branches. Secondly, it discusses the impact of HA synthase, precursor supply, and fermentation conditions on the synthesis of ultra-high molecular weight HA. Finally, it summarizes the preparation strategies for low molecular weight HA, including physical and chemical methods, enzymatic methods, and microbial direct fermentation. The review summarizes the latest research progress regarding the challenges faced in the biosynthesis and molecular weight regulation of hyaluronic acid (HA): specifically, the insufficient molecular weight of high molecular weight HA, the weak synthesis capability of medium molecular weight HA, and the poor controllability of low molecular weight HA. It provides a systematic overview to enhance the understanding of HA biosynthesis and molecular weight regulation strategies, aiming to facilitate the efficient biosynthesis of HA with controllable molecular weights.

Key words: hyaluronic acid, molecular weight, biosynthesis, metabolic engineering, synthetic biology

摘要:

透明质酸(Hyaluronic acid, HA)是一种在化妆品、食品和医疗领域广泛应用的天然直链酸性粘多糖。根据分子量大小,HA可分为高、中、低三类,不同分子量的HA具有不同的功能和应用场景。随着微生物发酵技术取代传统动物组织提取法,HA工业化生产取得了巨大进步。然而,天然HA合成菌株兽疫链球菌的缺点如潜在致病性以及难以分子改造,限制了不同分子量HA的生物合成研究。近年来,随着特定分子量HA需求的不断增长,代谢工程和合成生物学技术已广泛应用于HA生物合成与分子量调控。本文首先分析了中高分子量HA合成的限制性因素,重点讨论了HA前体合成途径的基因调控及竞争支路的弱化。其次,探讨了HA合酶、前体供应和发酵条件对超高分子量HA合成的影响。最后,总结了低分子量HA的制备策略,包括物理化学法、酶法和微生物直接发酵法。本文综述了这些最新的研究进展,针对HA的生物合成与分子量调控面临的挑战:高分子量HA分子量不够高、中高分子量HA合成能力弱和低分子量HA分子量可控性差三方面展开系统性综述,加强对HA生物合成与分子量调控策略的理解,助力实现可控分子量HA的高效生物合成。

关键词: 透明质酸, 分子量, 生物合成, 代谢工程, 合成生物学

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