Synthesis of structurally defined chondroitin sulfate: Paving the way to the structure-activity relationship studies

Ji, Yuan; Zhang, Shilin; Qiao, Meng; Jiao, Ruoyu; Li, Jun; Song, Ping; Zhang, Xing; Huang, He

doi:10.1016/j.carbpol.2020.116796

Cited by 30 publications

(15 citation statements)

References 79 publications

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“…This approach is in line with a recent trend in protein engineering that focuses on construction of small and smart libraries while reducing the size of the mutation library and improving evolution efficiency (Li, Qu, Sun, & Reetz, 2019;Sun, Lonsdale, Ilie, Li, & Reetz, 2016). Compared to traditional mutagenesis, this method is more rational as it relies on tunnel identification (Song et al, 2020;Yuan et al, 2019), conformational dynamics (Yang et al, 2017), specific hotspot scanning (Xu , Cen, Singh, Fan, & Wu, 2019;, and saturation mutagenesis. Overall, this protein engineering strategy could greatly improve the performance of enzymes with a release channel or lid structure.…”

Section: Discussionmentioning

confidence: 63%

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Rational design of a highly efficient catalytic system for the production of 3′-phosphoadenosine-5′-phosphosulfate from ATP

Liu¹,

Chen²,

Zhong³

et al. 2021

Preprint

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The compound 3′-phosphoadenosine-5′-phosphosulfate (PAPS) serves as a sulfate group donor in the production of valuable sulfated compounds, such as glycosaminoglycan and oxamniquine. However, elevated costs and low conversion efficiency limit the industrial applicability of PAPS. Here, we designed and constructed an efficient and controllable catalytic system for the conversion of ATP (disodium salt) into PAPS without inhibition from by-products. In vitro and in vivo testing in Escherichia coli identified adenosine-5′-phosphosulfate kinase from Penicillium chrysogenum (PcAPSK) as the rate-limiting enzyme. Based on analysis of the catalytic steps and molecular dynamics simulations, a mechanism-guided “ADP expulsion” strategy was developed to generate an improved PcAPSK variant (L7), with a specific activity of 48.94 U·mg-1 and 73.27-fold higher catalytic efficiency (kcat/Km) that of the wild-type enzyme. The improvement was attained chiefly by reducing the ADP-binding affinity of PcAPSK, as well as by changing the enzyme’s flexibility and lid structure to a more open conformation. By introducing PcAPSK L7 in an in vivo catalytic system, 73.59 mM (37.32 g·L-1) PAPS was produced from 150 mM ATP in 18.5 h using a 3-L bioreactor. The achieved titer is the highest reported to date and corresponds to a 98.13% conversion rate. The proposed strategy will facilitate industrial production of PAPS as well as the engineering of similar enzymes.

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Section: Discussionmentioning

confidence: 63%

“…The compound 3'-phosphoadenosine-5'-phosphosulfate (PAPS) acts as a sulfate group donor in the production of glucosinolate, heparin, chondroitin sulfate, and oxamniquine (Ji et al, 2020;Zhang, Lin, Huang, & Linhardt, 2020). At present, PAPS can be produced either via metabolic or enzymatic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Rational design of a highly efficient catalytic system for the production of 3′-phosphoadenosine-5′-phosphosulfate from ATP

Liu¹,

Chen²,

Zhong³

et al. 2021

Preprint

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“…As a natural glycosaminoglycan, chondroitin sulfate (CS) is constituted by repeating disaccharides of d-glucuronic acid and N-acetyl-d-galactosamine. The resulting repeating disaccharide unit →4-β-GlcA-(1→3)-β-GalNAc-1→ can be sulfated to various extents, which is shown in Figure 4 [92]. The presence of CS has been found in marine organisms such as shark, squid, sea cucumber, skate and sturgeon [93][94][95][96][97].…”

Section: Chondroitin Sulfatementioning

confidence: 99%

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances

et al. 2020

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Atherosclerosis is a chronic disease characterized by lipid accumulation and chronic inflammation of the arterial wall, which is the pathological basis for coronary heart disease, cerebrovascular disease and thromboembolic disease. Currently, there is a lack of low-cost therapeutic agents that effectively slow the progression of atherosclerosis. Therefore, the development of new drugs is urgently needed. The research and development of marine-derived drugs have gained increasing interest from researchers across the world. Many marine organisms provide a rich material basis for the development of atherosclerotic drugs. This review focuses on the latest technological advances in the structures and mechanisms of action of marine-derived anti-atherosclerotic substances and the challenges of the application of these substances including marine polysaccharides, proteins and peptides, polyunsaturated fatty acids and small molecule compounds. Here, we describe the theoretical basis of marine biological resources in the treatment of atherosclerosis.

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“…Enzymes can be used to produce CS oligosaccharides by degrading CS polymers or by synthesizing CS oligosaccharides/polymers through polymerization. The main advantages of using enzymes over chemical approaches is that enzymes catalyze stereoselective and regioselective reactions, potentially resulting in homogeneous CS in an eco-friendlier and faster manner [ 136 , 137 ]. However, these enzymatic steps are often combined with chemical synthesis or modifications (chemoenzymatic strategies) to either provide synthetic precursors or to perform the sulfation step.…”

Section: Enzymatic and Chemoenzymatic Cs Productionmentioning

confidence: 99%

“…However, these enzymatic steps are often combined with chemical synthesis or modifications (chemoenzymatic strategies) to either provide synthetic precursors or to perform the sulfation step. The depolymerizing/ degrading enzymes and the polysaccharide substrates used are relatively inexpensive [136] . However, the commercial polysaccharides are usually from animal sources which raises the concerns already mentioned.…”

Section: Enzymatic and Chemoenzymatic Cs Productionmentioning

confidence: 99%