Endophytic Akanthomyces sp. LN303 from Edelweiss Produces Emestrin and Two New 2‑Hydroxy‑4 Pyridone Alkaloids

In the search for
new antibiotics, several fungal endophytes were
isolated from the medicinal plant Leontopodium nivale subsp. alpinum (Edelweiss). The extract from one
of these fungi classified as Akanthomyces sp. displayed broad-spectrum antibiotic activity against gram-negative
bacteria and fungi. Further investigation into the composition of
this extract using bioactivity-guided fractionation, HRMS, and nuclear
magnetic resonance revealed two new 4-hydroxy-2-pyridone alkaloids
(1, 2) and emestrin (3), an
epidithiodioxopiperazine not previously known to be produced by a
member of Cordycipitaceae. Further testing of purified compounds 1 and 2 proved that they are devoid of antibiotic
activity, and all the activities observed in the crude extract could
be assigned to emestrin (3), whose configuration was
confirmed by crystallographic data. This study demonstrates, for the
first time, that endophytic fungi from Edelweiss can produce new compounds,
prompting further investigation into them for drug discovery.