Abstract. Secondary metabolites are small molecules produced by all corners of life, often with specialized bioactive functions with clinical and environme

A secondary metabolite sensitizes competitor Bacillus subtilis to a wide panel of lytic phages by sequestering iron and preventing the activation of Spo0A.

Streptomyces natural product exploration is impeded by the paucity of genetic editing tools available. Here, the authors engineer endogenous type I-E CRISPR into a series of transcriptional regulation...

Two clinical trials are currently underway in the U.S. to evaluate the effect of rapamycin on Long COVID and myalgic encephalomyelitis (ME) — one at Mount Sinai’s Cohen Center for Recovery from Comple...

Streptomycetes hold immense potential for discovering novel bioactive molecules for applications in medicine or sustainable agriculture. However, high-throughput exploration is hampered by the current...

The production of the anticancer drug paclitaxel depends on the extraction of the intermediate baccatin III from Taxus species. This Review highlights recent progress in genome-level analysis of pacli...

A concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20-epi-veratramine has been accom-plished. A Horner-Wadsworth-Emmons olefination joins two chiral building blocks of ap...

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

Biosynthesis of antimicrobial phytoalexin glyceollins in soybean is complicated and elusive. Here Xie et al. report a plant chassis for high-yield isoflavonoid production, leading to the identificatio...

Biosynthetic pathways of specialized metabolites utilize protein–protein interactions (PPIs) to facilitate metabolic flux and sequester reactive intermediates. The monoterpene indole alkaloid pathway of Catharanthus roseus contains several metabolic branch points that may be mediated via transient PPIs. We investigated one branch point of this pathway that is responsible for the conversion of the intermediate dehydrosecodine into three possible cyclized alkaloid scaffolds, which act as intermediates en route to medicinally important alkaloids, such as vinblastine. We verified previously observed PPIs between reductase-cyclase pairs and additionally uncovered PPIs between evolutionarily related protein homologues. Through structural analysis of dehydrosecodine cyclases, we identified surface residues that appear to mediate interaction with the upstream reductase. We then demonstrated, via in vitro competition assays, that these residues impact the distribution of downstream products. These results highlight the significance of transient PPIs in the control and regulation of specialized metabolite pathways.

Lactobacillus acidophilus ATCC 4356 (LA), a key probiotic in the human gut microbiota, offers severa

Despite the significance of nicotine, a neuroactive alkaloid produced by tobacco, its biosynthesis has remained elusive. Here, the authors report the in vitro and in planta reconstruction of a fo...