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Hyaluronic acid (HA), a natural linear acidic polysaccharide composed of disaccharide units of D-glucuronic acid (D-GlcA) and N-acetylglucosamine (N-GlcNAc), has been widely used in the cosmetic and medical fields. HAs with different molecular weights exhibit distinct biophysical properties. While high molecular weight HAs have stronger viscoelasticity and resistance to degradation, low molecular weight HAs demonstrate enhanced biological functions. Significant progress has been made for the industrial production of HAs, with the shift from traditional extraction from animal tissues to microbial fermentation. However, the use of the natural HA-producing species Streptococcus zooepidemicus presents challenges, such as potential pathogenicity and difficulties in molecular modifications, which limit the study on the biosynthesis of HAs with varying molecular weights. Recently, the increasing demand for specific molecular weight HAs has driven the application of metabolic engineering and synthetic biology techniques for their biosynthesis and molecular weight regulation. By identifying the key factors involved in the processes, researchers have developed various strategies to optimize the synthesis of HAs and control their molecular weights. This article first analyzes the limiting factors in the synthesis of medium and high molecular weight HAs, focusing on the genetic regulation on the synthesis pathways of HA precursors 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 HAs. Finally, it summarizes the preparation strategies for low molecular weight HAs, including physical and chemical methods, enzymatic methods, and microbial direct fermentation as well. The review summarizes the latest research progress regarding challenges faced in the biosynthesis and molecular weight regulation of HAs: specifically, the insufficient molecular weight of high molecular weight HAs, the weak synthesis capability of medium molecular weight HAs, and the poor controllability of low molecular weight HAs. It provides a systematic overview on enhancing the understanding of strategies for HA biosynthesis and molecular weight regulation, aiming to facilitate the efficient biosynthesis of HAs with controlled molecular weights.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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