In this week's Science, a group of European scientists reveals the heretofore unknown steps in the process by which the Madagascar periwinkle produces vinblastine, a potent anticancer agent that the flowering plant makes in small quantities. While most of the 31 enzymatic reactions involved in vinblastine production were known, two remained a mystery. By screening RNA data, the researchers identify two enzymes — dubbed tabersonine synthase (TS) and catharanthine synthase (CS) — as the missing links in the process. When they inhibit the genes that encode these enzymes in Madagascar periwinkles, the plants do not produce vinblastine. Additional analysis uncovered the other enzymes that work with TS and CS in the vinblastine-production process.
Also in Science, an international research team reports the identification of the genes essential to the human malaria parasite Plasmodium falciparum. Using transposon mutagenesis of the parasite in an approach that exploit its AT-rich genome, the investigators generate over 38,000 mutants "saturating the genome and defining mutability and fitness costs for over 87 percent of genes." Of the 5,399 genes analyzed, the scientists pinpoint 2,680 as essential for optimal growth of the parasite during stages when it infects human blood — including ones associated with drug resistance, ones that represent leading vaccine candidates, and ones of unknown function. Notably, some of the essential genes are expressed at high levels through both the asexual and sexual life cycle phases, suggesting that they may be critical throughout the stages when P. falciparum infects mosquito vectors and humans — making them particularly attractive drug targets.