ArticleThe FEBS journal2015
'Dopamine-first' mechanism enables the rational engineering of the norcoclaurine synthase aldehyde activity profile.
Article in The FEBS journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 76 citations in OpenAlex.
- Recent Progress in Catalytic Asymmetric Pictet-Spengler Reaction to Construct 1,1-Disubstituted Scaffolds.Synthesis · 2026Article
- Transaminase and Norcoclaurine Synthase One-Pot Cascades Towards (1S)-Tetrahydroisoquinolines.Chembiochem : a European journal of chemical biology · 2026Article
- Understanding the Enzyme (Journal of chemical information and modeling · 2024Article
- A transaminase-mediated aldol reaction and applications in cascades to styryl pyridines.Catalysis science & technology · 2024Article
- Computational mechanistic investigation of the kinetic resolution of α-methyl-phenylacetaldehyde by norcoclaurine synthase.Communications chemistry · 2024Article
- Promising approaches for simultaneous enhancement of medicinally significant benzylisoquinoline alkaloids in opium poppy.Frontiers in plant science · 2024Review
- Elucidation of the (R)-enantiospecific benzylisoquinoline alkaloid biosynthetic pathways in sacred lotus (Nelumbo nucifera).Scientific reports · 2023Article
- C-1 Substituted isoquinolines potentiate the antimycobacterial activity of rifampicin and ethambutol.Frontiers in antibiotics · 2023Article
- Enzymatic synthesis of benzylisoquinoline alkaloids using a parallel cascade strategy and tyrosinase variants.Nature communications · 2022Article
- Genome-Wide Transcriptomic Analysis of the Effects of Infection with the Hemibiotrophic FungusPlants (Basel, Switzerland) · 2022Article
- The Transformative Power of Biocatalysis in Convergent Synthesis.Journal of the American Chemical Society · 2022Review
- Transcriptome analysis of Leucojum aestivum and identification of genes involved in norbelladine biosynthesis.Planta · 2022Article
- Redesigning Enzymes for Biocatalysis: Exploiting Structural Understanding for Improved Selectivity.Frontiers in molecular biosciences · 2022Review
- Multienzyme One-Pot Cascades Incorporating Methyltransferases for the Strategic Diversification of Tetrahydroisoquinoline Alkaloids.Angewandte Chemie (International ed. in English) · 2021Article
- Multienzyme One-Pot Cascades Incorporating Methyltransferases for the Strategic Diversification of Tetrahydroisoquinoline Alkaloids.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- Review
- Biosynthesis and synthetic biology of psychoactive natural products.Chemical Society reviews · 2021Review
- Peroxisomes: A New Hub for Metabolic Engineering in Yeast.Frontiers in bioengineering and biotechnology · 2021Article
- Peroxisome compartmentalization of a toxic enzyme improves alkaloid production.Nature chemical biology · 2021Article
- Single step syntheses of (1S)-aryl-tetrahydroisoquinolines by norcoclaurine synthases.Communications chemistry · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet-Spengler condensation of dopamine and an aldehyde, forming a substituted (S)-tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity has led to NCS being used for both in vitro biocatalysis and in vivo recombinant metabolism. Future engineering of NCS activity to enable the synthesis of diverse tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and kinetics. We assess two proposed mechanisms for NCS activity: (a) one based on the holo X-ray crystal structure and (b) the 'dopamine-first' mechanism based on computational docking. Thalictrum flavum NCS variant activities support the dopamine-first mechanism. Suppression of the non-enzymatic background reaction reveals novel kinetic parameters for NCS, showing it to act with low catalytic efficiency. This kinetic behaviour can account for the ineffectiveness of recombinant NCS in in vivo systems, and also suggests NCS may have an in planta role as a metabolic gatekeeper. The amino acid substitution L76A, situated in the proposed aldehyde binding site, results in the alteration of the enzyme's aldehyde activity profile. This both verifies the dopamine-first mechanism and demonstrates the potential for the rational engineering of NCS activity.
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