Abstract Monoterpene indole alkaloids (MIAs) are a large, structurally diverse class of bioactive natural products. These compounds are biosynthetically derived from a stereoselective Pictet–Spengler condensation that generates a tetrahydro-β-carboline scaffold characterized by a 3 S stereocenter. However, a subset of MIAs contains a noncanonical 3 R stereocenter. Here we report the basis for 3 R -MIA biosynthesis in Mitragyna speciosa (kratom). We discover the presence of the iminium species (20 S )-3-dehydrocory…

Abstract Iridoids are specialized monoterpenes ancestral to asterid flowering plants 1,2 that play key roles in defence and are also essential precursors for pharmacologically important alkaloids 3,4 . The biosynthesis of all iridoids involves the cyclization of the reactive biosynthetic intermediate 8-oxocitronellyl enol. Here, using a variety of approaches including single-nuclei sequencing, we report the discovery of iridoid cyclases from a phylogenetically broad sample of asterid species that synthesize iridoi…

Iridoids are specialized monoterpenes ancestral to asterid flowering plants (Albach et al , 2001; Stull et al , 2018). Iridoids play key roles in plant defense and are also essential precursors for pharmacologically important alkaloids (Dobler et al , 2011; Eisner, 1964). The biosynthesis of all iridoids involves the cyclization of a reactive enol intermediate. While this cyclization occurs spontaneously at low yields, it has long been hypothesized that a dedicated enzyme is involved in this process (Geu-Flores et…

The UbiX/UbiD system is widespread in microbes and responsible for the reversible decarboxylation of unsaturated carboxylic acids. The UbiD enzyme catalyzes this unusual reaction using a prenylated flavin (prFMN) as cofactor, the latter formed by the flavin prenyltransferase UbiX. A detailed picture of the biochemistry of flavin prenylation, oxidative maturation, and covalent catalysis underpinning reversible decarboxylation is emerging. This reveals the prFMN cofactor can undergo a wide range of transformations, …

Allylic amines are a versatile class of synthetic precursors of many valuable nitrogen-containing organic compounds, including pharmaceuticals. Enzymatic allylic amination methods provide a sustainable route to these compounds but are often restricted to allylic primary amines. We report a biocatalytic system for the reductive <i>N</i>-allylation of primary and secondary amines, using biomass-derivable cinnamic acids. The two-step one-pot system comprises an initial carboxylate reduction step catalyzed by a carbox…