Figure 1 - Biochemistry of BBE and homologous enzymes.

(a) BBE catalyzes the conversion of (S)-reticuline to (S)-scoulerine, a cyclization reaction that involves the formation of the so-called berberine bridge that links the benzyl and isoquinoline rings of the substrate. Reticuline is synthesized from L-tyrosine, whereas the product of the BBE reaction represents the precursor of a wide and diverse group of alkaloids that have various biological activities. (b) Simplified scheme of the catalytic mechanism of BBE proposed by Winkler et al.³. (c) Plant genomes exhibit a number of BBE homologs whose biological activities remain mostly to be uncovered. Among the BBE homologs, there are enzymes that take part in the biosynthesis of cannabinoids. Remarkably, these synthases act on molecules that substantially differ from reticuline, highlighting the biocatalytic potential and diversity of the family of BBE-related enzymes.