Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches

Electrochemical study of some 2,5-dimethoxyamphetamine derivatives

A set of 2,5-dimethoxyamphetamines differing in their substitution at C4 was studied by differential pulse voltammetry and linear scan cyclic voltammetry in aqueous media. These experiments showed a single oxydation peak for each of the compounds studied. This peak is attributed to oxidation of the aromatic ring with formation of a radical cation stabilized by the methoxy group bonded to the benzene ring