Biosynthesis of AS2077715 and Funiculosin: Pathway Reconstitution and Identification of Enzymes that Form the All- Cyclopentanetetraol Moiety.

The complete biosynthetic pathways of the potent antifungals AS2077715 () and funiculosin () are reconstituted and characterized. A five-enzyme cascade, including a multifunctional flavin-dependent monooxygenease and a repurposed methyltransferase, is involved to perform the dearomatization, stereoselective ring contraction, and redox transformations to morph a hydroxyphenyl-containing precursor into the unusual all- cyclopentanetetraol moiety.

Biosynthesis of the Fusarium Mycotoxin (-)-Sambutoxin.

4-Hydroxy-2-pyridone alkaloids have attracted attention for synthetic and biosynthetic studies due to their broad biological activities and structural diversity. Here, we elucidated the pathway and chemical logic of (-)-sambutoxin () biosynthesis. In particular, we uncovered the enzymatic origin of the tetrahydropyran moiety and showed that the -hydroxyphenyl group is installed via a late-stage, P450-catalyzed oxidation of the phenylalanine-derived side chain rather than via a direct incorporation of tyrosine.

DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis.

Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis.