Lachnone A

Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual β-lactone-fused bicycle is derived from an aryl ring moiety by an oxidative ring-expansion prior to an intramolecular cyclization. Herein, we report the discovery of the cyclase VibC which belongs to the α/β-hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the Ser-His-Asp catalytic triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic β-lactone. This presents a naturally occurring, new enzymatic reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical-diversity expansion of natural products.

Lasiodiplactone A (1), an unprecedented lactone, was obtained from the mangrove endophytic fungus Lasiodiplodia theobromae ZJ-HQ1. The structure of 1 was established by analysis of NMR spectroscopic data and electronic circular dichroism (ECD) spectra. Lasiodiplactone A (1) was the first example of lactone that possesses a unique tetracyclic system (12/6/6/5) of RAL12(12-membered β-resorcylic acid lactone) with a pyran ring and a furan ring. A possible biogenetic pathway for 1 was proposed. Compound 1 showed anti-inflammatory activity by inhibiting nitric oxide (NO) production in lipopolysaccharide activated in RAW264.7 cells with IC50value of 23.5 μM and exhibited potential α-glucosidase inhibitory activity with IC50values of 29.4 μM.

Cochliomycin G (1), a new 14-membered resorcylic acid lactone, together with six known analogues (2-7), was isolated from the culture broth of a marine-derived fungusCochliobolus lunatus. The planar structure of1was established by extensive NMR spectroscopy, and the absolute configuration was elucidated by the combination of empirical rules, CD data, and13C chemical shift calculations. Compound1exhibited potent antifouling activity againstChlorella vulgaris,Chaetoceros socialis, andNavicula exigua, with EC50values of 1.09, 0.92, and 0.61μg/mL, respectively.