Insights into the source, mechanism and biotechnological applications of hyaluronidases

Zhang, Yue-Sheng; Gong, Jin‐Song; Yao, Zhi-Yuan; Jiang, Jiayu; Su, Chang; Li, Heng; Kang, Chuan-Li; Liu, Lei; Xu, Zhenghong; Shi, Jin‐Song

doi:10.1016/j.biotechadv.2022.108018

Cited by 14 publications

(5 citation statements)

References 204 publications

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“…13 The enzymatic degradation of nonsulfated HA is achieved by bacterial lyases rather than extraction from animal tissues, using naturally producing or genetically engineered microbial strains, and used as a starting material through digestion with hyaluronidases. 14 Partial digestion with mammalian hyaluronidases generates a wide range of HA oligosaccharide lengths. Mammalian hyaluronidases yield tetra/hexasaccharides because these enzymes display hydrolytic and transglycosylation activities simultaneously.…”

Section: Nomenclaturementioning

confidence: 99%

Glycosaminoglycans: What Remains To Be Deciphered?

Pérez

Makshakova

Angulo

et al. 2023

JACS Au

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Glycosaminoglycans (GAGs) are complex polysaccharides exhibiting a vast structural diversity and fulfilling various functions mediated by thousands of interactions in the extracellular matrix, at the cell surface, and within the cells where they have been detected in the nucleus. It is known that the chemical groups attached to GAGs and GAG conformations comprise “glycocodes” that are not yet fully deciphered. The molecular context also matters for GAG structures and functions, and the influence of the structure and functions of the proteoglycan core proteins on sulfated GAGs and vice versa warrants further investigation. The lack of dedicated bioinformatic tools for mining GAG data sets contributes to a partial characterization of the structural and functional landscape and interactions of GAGs. These pending issues will benefit from the development of new approaches reviewed here, namely (i) the synthesis of GAG oligosaccharides to build large and diverse GAG libraries, (ii) GAG analysis and sequencing by mass spectrometry (e.g., ion mobility-mass spectrometry), gas-phase infrared spectroscopy, recognition tunnelling nanopores, and molecular modeling to identify bioactive GAG sequences, biophysical methods to investigate binding interfaces, and to expand our knowledge and understanding of glycocodes governing GAG molecular recognition, and (iii) artificial intelligence for in-depth investigation of GAGomic data sets and their integration with proteomics.

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Section: Nomenclaturementioning

confidence: 99%

Glycosaminoglycans: What Remains To Be Deciphered?

Pérez

Makshakova

Angulo

et al. 2023

JACS Au

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“…Table 2 shows the major HA-based hydrogels used in treating DUs over the last five years. However, despite the many advantages of HA, unmodified HA is rapidly degraded by hyaluronidase in body fluids, resulting in a short half-life in vivo [ 158 ]. Therefore, HA must be chemically modified before it can be used in tissue engineering and drug delivery.…”

Section: Advanced Polymer Hydrogels For Dusmentioning

confidence: 99%

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

Wei

et al. 2023

Biomater Res

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Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. Graphical Abstract This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

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“…Hyaluronidase is a group of carbohydrate-active enzymes that possess major degradation activity toward hyaluronan (HA) (Yao et al 2023;Zhang et al 2022). Hyaluronidases are widely applied in the food industry, cosmetic industry, and medical field.…”

Section: Introductionmentioning

confidence: 99%

Engineering protein translocation and unfolded protein response enhanced human PH-20 secretion in Pichia pastoris

Zhang,

Gong,

Jiang

et al. 2024

Appl Microbiol Biotechnol

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Hyaluronidases catalyze the degradation of hyaluronan (HA), which is finding rising applications in medicine, cosmetic, and food industries. Recombinant expression of hyaluronidases in microbial hosts has been given special attention as a sustainable way to substitute animal tissue-derived hyaluronidases. In this study, we focused on optimizing the secretion of hyaluronidase from Homo sapiens in Pichia pastoris by secretion pathway engineering. The recombinant hyaluronidase was first expressed under the control of a constitutive promoter P GCW14 . Then, two endoplasmic reticulum-related secretory pathways were engineered to improve the secretion capability of the recombinant strain. Signal peptide optimization suggested redirecting the protein into co-translational translocation using the ost1-proα signal sequence improved the secretion level by 20%. Enhancing the co-translational translocation by overexpressing signal recognition particle components further enhanced the secretory capability by 48%. Then, activating the unfolded protein response by overexpressing a transcriptional factor ScHac1p led to a secreted hyaluronidase activity of 4.06 U/mL, which was 2.1-fold higher than the original strain. Finally, fed-batch fermentation elevated the production to 19.82 U/mL. The combined engineering strategy described here could be applied to enhance the secretion capability of other proteins in yeast hosts. Key points• Improving protein secretion by enhancing co-translational translocation in P. pastoris was reported for the first time.• Overexpressing Hac1p homologous from different origins improved the rhPH-20 secretion.• A 4.9-fold increase in rhPH-20 secretion was achieved after fermentation optimization and fed-batch fermentation.

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Insights into the source, mechanism and biotechnological applications of hyaluronidases

Cited by 14 publications

References 204 publications

Glycosaminoglycans: What Remains To Be Deciphered?

Glycosaminoglycans: What Remains To Be Deciphered?

Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

Engineering protein translocation and unfolded protein response enhanced human PH-20 secretion in Pichia pastoris

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