A Catch-Release Strategy for the Genomics-Driven Discovery of Antiproliferative Furan-Functionalized Peptides.

Furan-functionalized peptides are of significant pharmacological interest due to their pronounced bioactivities and unique potential for orthogonal bioconjugation and derivatization. However, naturally occurring peptides with furyl side chains are exceedingly rare. This study presents a streamlined method to predict and assess the microbial production of peptides incorporating 3-furylalanine (Fua) moieties.

Using Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) as a Rescue Strategy in Severe Postpartum Hemorrhage: A Case Report.

Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality. Routine treatment of PPH includes uterotonics, tranexamic acid, curettage, uterine (balloon) tamponade, compression sutures, uterine artery ligation, and, if available, transcatheter arterial embolization (TAE). In cases of severe PPH refractory to standard medical and surgical management, hysterectomy is usually the ultima ratio, and is equally associated with a higher rate of complications.

Direct α-Hydroxy Acid Loading onto a Bacterial Thiotemplate Assembly Line via a Multienzyme Gateway.

Various nonribosomal peptide synthetases (NRPSs) create structural and functional diversity by incorporating α-hydroxy acids into peptide backbones. Trigonic acid, an unusual cyclopropanol-substituted hydroxy acid, is the source of the molecular warhead of malleicyprol, a critical virulence factor of human and animal pathogens of the Burkholderia pseudomallei (BP) group. The process of selecting and loading this building block remained enigmatic as the NRPS module designated for this task is incomplete.

Analysis of the Valgamicin Biosynthetic Pathway Reveals a General Mechanism for Cyclopropanol Formation across Diverse Natural Product Scaffolds.

Cyclopropanol rings are highly reactive and may function as molecular "warheads" that affect natural product bioactivity. Yet, knowledge on their biosynthesis is limited. Using gene cluster analyses, isotope labeling, and in vitro enzyme assays, we shed first light on the biosynthesis of the cyclopropanol-substituted amino acid cleonine, a residue in the antimicrobial depsipeptide valgamicin C and the cytotoxic glycopeptide cleomycin A2.