ArticleNature communications2024
Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Advances in chemoenzymatic synthesis of glycosaminoglycans and proteoglycans.Current opinion in chemical biology · 2026Review
- The Structure-Activity Relationship and Anticoagulation Mechanism of Polyglycerol Sulfates of Different Architectures.Biomacromolecules · 2026Article
- Chemical Strategies for Controlling Sulfation in Biomacromolecules.ACS chemical biology · 2026Review
- Synthetic biology for heparin biomanufacturing.Bioresources and bioprocessing · 2026Review
- Natural polysaccharides as immune adjuvants to overcome immune checkpoint inhibitor resistance: mechanistic insights, clinical evidence, and translational challenges.Frontiers in immunology · 2026Review
- Metabolic reprogramming and computation-aided protein engineering for high-level de novo biosynthesis for 2-phenylethanol inSynthetic and systems biotechnology · 2025Article
- Dermatan Sulfate: Structure, Biosynthesis, and Biological Roles.Biomolecules · 2025Review
- Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library.Nature communications · 2025Article
- Recent Advances in Polysaccharide-Based Hydrogels for Tumor Immunotherapy.Gels (Basel, Switzerland) · 2025Review
- Multifaceted Heparin: Diverse Applications beyond Anticoagulant Therapy.Pharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.
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