Spirodalesol, an NLRP3 Inflammasome Activation Inhibitor

Autoimmune and inflammatory diseases are associated with inappropriate activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, but suitable inhibitors against such improper activations remain scarce. Here, spirodalesol (<b>1</b>) from Daldinia eschscholzii was structurally characterized and is biosynthetically proposed as an NLRP3 inflammasome activation inhibitor with an unprecedented carbon skeleton

Curindolizine, an Anti-Inflammatory Agent Assembled via Michael Addition of Pyrrole Alkaloids Inside Fungal Cells

<i>Curvularia</i> sp. IFB-Z10, a white croaker-associated fungus, generates a skeletally unprecedented indolizine alkaloid named curindolizine (<b>1</b>), which displays an anti-inflammatory action in lipopolyssacharide (LPS)-induced RAW 264.7 macrophages with an IC₅₀ value of 5.31 ± 0.21 μM. The enzymatic transformation test demonstrated that the unique curindolizine architecture was most likely produced by the regiospecific in-cell Michael addition reaction between pyrrole alkaloids, curvulamine, and 3,5-dimethylindolizin-8­(5<i>H</i>)-one

Muta-mycosynthesis of Naphthalene Analogs

A mutasynthetic strategy is introduced for the mycosynthesis of naphthalene-based molecules (mutadalesols A–F) with directed substitution patterns and new frameworks by generating and using the <i>ΔpksTL</i> mutant strain of <i>Daldinia eschscholzii.</i> (±)-Mutadalesol A and its (+)-enantiomer are cytotoxic, and its (−)-enantiomer inhibits Toll-like receptor 5 (TLR5). The in-culture reactability of fungal oligoketide intermediates with 5-aminonaphthalen-1-ol (ANL) is demonstrated, shedding light on bioorthogonal accesses to unnatural molecule libraries valuable in drug discovery pipelines

Curvulamine, a New Antibacterial Alkaloid Incorporating Two Undescribed Units from a <i>Curvularia</i> Species

The white croaker (<i>Argyrosomus argentatus</i>) derived <i>Curvularia</i> sp. IFB-Z10 produces curvulamine as a skeletally unprecedented alkaloid incorporating two undescribed extender units. Curvulamine is more selectively antibacterial than tinidazole and biosynthetically unique in the new extenders formed through a decarboxylative condensation between an oligoketide motif and alanine