Biosynthesis of Diverse Ephedra-Type Alkaloids via a Newly Identified Enzymatic Cascade.

Ephedra-type alkaloids represent a large class of natural and synthetic phenylpropanolamine molecules with great pharmaceutical values. However, the existing methods typically rely on chemical approaches to diversify the -group modification of Ephedra-type alkaloids. Herein, we report a 2-step enzymatic assembly line for creating structurally diverse Ephedra-type alkaloids to replace the conventional chemical modification steps.

Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance.

Mutations in a Plasmodium de-ubiquitinase UBP1 have been linked to antimalarial drug resistance. However, the UBP1-mediated drug-resistant mechanism remains unknown. Through drug selection, genetic mapping, allelic exchange, and functional characterization, here we show that simultaneous mutations of two amino acids (I1560N and P2874T) in the Plasmodium yoelii UBP1 can mediate high-level resistance to mefloquine, lumefantrine, and piperaquine.