Norcoclaurine Synthase: Mechanism of an Enantioselective Pictet-Spengler Catalyzing Enzyme

Molecules

Alessandra Bonamore¹  Marco Barba¹  Bruno Botta¹  Alberto Boffi¹ 

[1] ¹Dipartimento di Scienze Biochimiche, Università “Sapienza” P. Aldo Moro 5, 00185, Rome, Italy ²Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università “Sapienza” P. Aldo Moro 5, 00185, Rome, Italy

关键词: norcoclaurine synthase;    (S)-norcoclaurine;    Pictet-Spengler condensation;    bifunctional catalysis;    green synthetic process;   

DOI  :  10.3390/molecules15042070

来源: mdpi

【 摘 要 】

The use of bifunctional catalysts in organic synthesis finds inspiration in the selectivity of enzymatic catalysis which arises from the specific interactions between basic and acidic amino acid residues and the substrate itself in order to stabilize developing charges in the transition state. Many enzymes act as bifunctional catalysts using amino acid residues at the active site as Lewis acids and Lewis bases to modify the substrate as required for the given transformation. They bear a clear advantage over non-biological methods for their ability to tackle problems related to the synthesis of enantiopure compounds as chiral building blocks for drugs and agrochemicals. Moreover, enzymatic synthesis may offer the advantage of a clean and green synthetic process in the absence of organic solvents and metal catalysts. In this work the reaction mechanism of norcoclaurine synthase is described. This enzyme catalyzes the Pictet-Spengler condensation of dopamine with 4-hydroxyphenylacetaldehyde (4-HPAA) to yield the benzylisoquinoline alkaloids central precursor, (S)-norcoclaurine. Kinetic and crystallographic data suggest that the reaction mechanism occurs according to a typical bifunctional catalytic process.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.