Biology subjects

Morweiser, C.

Publications and source records attributed to Morweiser, C..

3 recordsLinked to original sources

bioRxiv2026

Discovery of a Plant Pictet-Spenglerase with R-Stereoselectivity

The class-defining monoterpenoid indole alkaloid (MIA) scaffold strictosidine is generated by condensation of tryptamine and secologanin by the Pictet-Spenglerase strictosidine synthase (STR). All previously characterized STR orthologs are strictly 3S-stereoselective. Here, we report that the medicinal plant species Pogonopus speciosus (Rubiaceae) accumulates the 3R epimer vincosidic acid produced by a an ortholog of STR. This ortholog, named here Epi-STR, exclusively produces the 3R configuration and is capable of accepting both secologanic acid and the methylester secologanin as aldehyde substrates. Using comparative phylogenetic and structural analyses, we determine the amino acid residues that confer stereoselectivity. Through rational design of reciprocal amino acid substitutions, we achieved switches in stereoselectivity in a canonical STR and in Epi-STR. The stereoselectivity of the engineered mutants is also dependent on the identity of the aldehyde substrate. Notably, previous and extensive engineering efforts have failed to switch the stereo-selectivity of STR. Therefore, this discovery now allows cost-effective epimer-pure access to the R-epimer, and offers mechanistic insights into the enzyme stereoselectivity of this important reaction. This work also highlights the importance of phytochemical analyses of poorly described plant species.

biochemistry↗

bioRxiv2025

Discovery of iridoid cyclase completes the iridoid pathway in asterids

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 al, 2012; Lichman et al, 2019b). Here, we report the discovery of asterid iridoid cyclases (ICYC). We show that these enzymes catalyze cyclization of the reactive intermediate to form the two major iridoid stereoisomers found in plants. Our work uncovers the last missing key step in the otherwise well-characterized iridoid biosynthesis pathway in asterids. This discovery unlocks the possibility to generate previously inaccessible iridoid stereoisomers, which will enable metabolic engineering for the sustainable production of valuable iridoid and iridoid-derived compounds.

plant biology↗

bioRxiv2024

Independent evolution of ipecac alkaloid biosynthesis

Ipecac alkaloids are medicinal monoterpenoid-derived tetrahydroisoquinoline alkaloids found in two distantly related plants: Carapichea ipecacuanha (Gentianales) and Alangium salviifolium (Cornales). We have elucidated ipecac alkaloid biosynthesis in both species, conclusively demonstrating that biosynthesis of the structurally complex ipecac alkaloid protoemetine has evolved independently. We show that although protoemetine biosynthesis proceeds via the same chemical logic in both species, each plant uses a distinct monoterpene precursor. Moreover, we provide evidence that both plants initiate ipecac biosynthesis by a non-enzymatic Pictet-Spengler reaction, and we elucidate the biosynthetic fate of both the 1R and 1S stereoisomers that are produced in this non-stereoselective reaction. Phylogenetic analyses clearly show independent pathway evolution through parallel and convergently evolved enzymes. This work provides insight into how nature can capitalize on highly reactive starting substrates, the manner in which multi-step pathways can arise, and also lays the foundation for metabolic engineering of these important medicinal compounds.

plant biology↗