ArticleScientific reports2018
Catalysis of amorpha-4,11-diene synthase unraveled and improved by mutability landscape guided engineering.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Regulatory architecture of high-altitude adaptation in Artemisia: from signal perception to specialized metabolism.Plant cell reports · 2026Review
- Advances in semi-rational design of terpene synthases and their modifying enzymes.AMB Express · 2025Review
- Characterization of the Cubamyces Menziesii Terpenome.Chembiochem : a European journal of chemical biology · 2025Article
- Article
- Advanced metabolic engineering strategies for increasing artemisinin yield inHorticulture research · 2024Article
- Application of valencene and prospects for its production in engineered microorganisms.Frontiers in microbiology · 2024Review
- Decoding Catalysis by Terpene Synthases.ACS catalysis · 2023Review
- Making Enzymes Suitable for Organic Chemistry by Rational Protein Design.Chembiochem : a European journal of chemical biology · 2022Review
- Toward improved terpenoids biosynthesis: strategies to enhance the capabilities of cell factories.Bioresources and bioprocessing · 2022Review
- Amorpha-4,11-diene synthase: a key enzyme in artemisinin biosynthesis and engineering.aBIOTECH · 2021Review
- Kinetic studies and homology modeling of a dual-substrate linalool/nerolidol synthase from Plectranthus amboinicus.Scientific reports · 2021Article
- Positioning Bacillus subtilis as terpenoid cell factory.Journal of applied microbiology · 2021Review
- Engineering of Multiple Modules to Improve Amorphadiene Production inJournal of agricultural and food chemistry · 2021Article
- Protein engineering for natural product biosynthesis and synthetic biology applications.Protein engineering, design & selection : PEDS · 2021Review
- Synthetic biology, combinatorial biosynthesis, and chemo‑enzymatic synthesis of isoprenoids.Journal of industrial microbiology & biotechnology · 2020Review
- Creation of RANKL mutants with low affinity for decoy receptor OPG and their potential anti-fibrosis activity.The FEBS journal · 2019Article
- Identifying and engineering the ideal microbial terpenoid production host.Applied microbiology and biotechnology · 2019Review
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Amorpha-4,11-diene synthase (ADS) cyclizes the substrate farnesyl pyrophosphate to produce amorpha-4,11-diene as a major product. This is considered the first committed and rate-limiting step in the biosynthesis of the antimalarial artemisinin. Here, we utilize a reported 3D model of ADS to perform mutability landscape guided enzyme engineering. A mutant library of 258 variants along sixteen active site residues was created then screened for catalytic activity and product profile. This allowed for identification of the role of some of these residues in the mechanism. R262 constrains the released pyrophosphate group along with magnesium ions. The aromatic residues (W271, Y519 and F525) stabilize the intermediate carbocations while T296, G400, G439 and L515 help with the 1,6- and 1,10-ring closures. Finally, W271 is suggested to act as active site base along with T399, which ensures regioselective deprotonation. The mutability landscape also helped determine variants with improved catalytic activity. H448A showed ~4 fold increase in catalytic efficiency and the double mutation T399S/H448A improved k
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