Norcoclaurine synthase: mechanism of an enantioselective pictet-spengler catalyzing enzyme.
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.
Bonamore
Alessandra
A
Dipartimento di Scienze Biochimiche, Università Sapienza P. Aldo Moro 5, Rome, Italy.
Barba
Marco
M
Botta
Bruno
B
Boffi
Alberto
A
Macone
Alberto
A
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000470:Alkaloids / Q000096:biosynthesis / Q000138:chemical synthesis*; D044182:Benzylisoquinolines / Q000138:chemical synthesis* / Q000378:metabolism; D055162:Biocatalysis; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry*; D003461:Crystallography; D004298:Dopamine / Q000737:chemistry*; D019800:Phenol; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis*
D000470:Alkaloids; D044182:Benzylisoquinolines; D044005:Tetrahydroisoquinolines; D019800:Phenol; C097891:4-hydroxyphenylacetaldehyde; D019731:Carbon-Nitrogen Ligases; C450500:norcoclaurine synthase; D000079:Acetaldehyde; C012348:higenamine; D004298:Dopamine