13 research outputs found
Acaulide, an Osteogenic Macrodiolide from <i>Acaulium</i> sp. H‑JQSF, an Isopod-Associated Fungus
Acaulide
(<b>1</b>), a macrodiolide with an unprecedented
framework, was characterized along with its shunt productsî—¸acaulones
A (<b>2</b>) and B (<b>3</b>)î—¸from the culture
of <i>Acaulium</i> sp. H-JQSF associated with the isopod <i>Armadillidium vulgare</i>. The spiro-linked 14-, 14-, and 6-membered
cycles of <b>1</b> arise likely from iterative intermolecular
Michael addition reactions. Biological evaluation in the prednisolone-induced
osteoporotic zebrafish demonstrated that <b>1</b> is antiosteoporotic
at 0.4 and 2.0 μM
Acaulins A and B, Trimeric Macrodiolides from <i>Acaulium</i> sp. H‑JQSF
Acaulin
A (<b>1</b>) and its macrolactone ring-opened congener
acaulin B (<b>2</b>) were characterized from the culture of <i>Acaulium</i> sp. H-JQSF (an isopod-associated fungus) as architecturally
undescribed trimeric macrodiolides, with the former being antiosteoporotic
at 0.4 μM in the prednisolone-induced osteoporotic zebrafish.
Identification of acaudiolic acid (<b>3</b>) as the monomeric
macrodiolide precursor facilitated the proposal of the acaulin biosynthetic
pathway
Citrofulvicin, an Antiosteoporotic Polyketide from <i>Penicillium velutinum</i>
Citrofulvicin (<b>1</b>), along
with its early shunt product
fulvionol (<b>2</b>), was characterized as a skeletally unprecedented
antiosteoporotic agent from a human sputum-derived fungus <i>Penicillium velutinum.</i> The unique citrofulvicin framework
is likely formed by a nonenzymatic intermolecular Diels–Alder
cycloaddition between heptaketide-based intermediates. Citrofulvicin
and fulvionol were demonstrated to be osteogenic at 0.1 μM in
the prednisolone-induced osteoporotic zebrafish
<i>p</i>-Terphenyl and Diterpenoid Metabolites from Endophytic <i>Aspergillus</i> sp. YXf3
Six new <i>p</i>-terphenyl derivatives, named
4″-deoxy-3-hydroxyterphenyllin (<b>1</b>), 4″-deoxy-5′-desmethyl-terphenyllin
(<b>2</b>), 5′-desmethylterphenyllin (<b>3</b>),
4″-deoxycandidusin A (<b>4</b>), 4,5-dimethoxycandidusin
A (<b>5</b>), and terphenolide (<b>6</b>), four new diterpenoids
with norcleistanthane (aspergiloid A (<b>12</b>) and aspergiloid
B (<b>13</b>)), cleistanthane (aspergiloid C (<b>14</b>)), and isopimarane (aspergiloid D (<b>15</b>)) type skeletons,
and five known <i>p</i>-terphenyl compounds (<b>7</b>–<b>11</b>) were isolated from the fermentation broth
of the plant endophytic fungus <i>Aspergillus</i> sp. Their
structures were elucidated on the basis of detailed spectroscopic
analysis and by comparison of their NMR data with those reported in
the literature. Compounds <b>4</b>, <b>6</b>,<b> 7</b>, and <b>9</b> displayed moderate neuraminidase inhibitory
activity with IC<sub>50</sub> values ranging from 4.34 to 9.17 μM
P450-Modified Ribosomally Synthesized Peptides with Aromatic Cross-Links
Cyclization of linear peptides is an effective strategy
to convert flexible molecules into rigid compounds, which is of great
significance for enhancing the peptide stability and bioactivity.
Despite significant advances in the past few decades, Nature and chemists’
ability to macrocyclize linear peptides is still quite limited. P450
enzymes have been reported to catalyze macrocyclization of peptides
through cross-linkers between aromatic amino acids with only three
examples. Herein, we developed an efficient workflow for the identification
of P450-modified RiPPs in bacterial genomes, resulting in the discovery
of a large number of P450-modified RiPP gene clusters. Combined with
subsequent expression and structural characterization of the products,
we have identified 11 novel P450-modified RiPPs with different cross-linking
patterns from four distinct classes. Our results greatly expand the
structural diversity of P450-modified RiPPs and provide new insights
and enzymatic tools for the production of cyclic peptides
Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus <i>Diaporthe</i> sp.
A new sesquiterpenoid, diaporol A (<b>1</b>), possessing
a unique tricyclic lactone framework, eight new drimane sesquiterpenoids,
diaporols B–I (<b>2</b>–<b>9</b>), and the
known compounds <b>10</b> and <b>11</b> were isolated
from a culture of the mangrove-derived endophyte <i>Diaporthe</i> sp. The absolute configurations of <b>1</b>–<b>5</b> were determined by low-temperature (100 K) single-crystal X-ray
diffraction with Cu Kα radiation. The compounds were evaluated
for cytotoxic activity; however, no compound showed significant cytotoxicity
against the tested cell lines at a concentration of 20 μM
Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus <i>Diaporthe</i> sp.
A new sesquiterpenoid, diaporol A (<b>1</b>), possessing
a unique tricyclic lactone framework, eight new drimane sesquiterpenoids,
diaporols B–I (<b>2</b>–<b>9</b>), and the
known compounds <b>10</b> and <b>11</b> were isolated
from a culture of the mangrove-derived endophyte <i>Diaporthe</i> sp. The absolute configurations of <b>1</b>–<b>5</b> were determined by low-temperature (100 K) single-crystal X-ray
diffraction with Cu Kα radiation. The compounds were evaluated
for cytotoxic activity; however, no compound showed significant cytotoxicity
against the tested cell lines at a concentration of 20 μM
Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus <i>Diaporthe</i> sp.
A new sesquiterpenoid, diaporol A (<b>1</b>), possessing
a unique tricyclic lactone framework, eight new drimane sesquiterpenoids,
diaporols B–I (<b>2</b>–<b>9</b>), and the
known compounds <b>10</b> and <b>11</b> were isolated
from a culture of the mangrove-derived endophyte <i>Diaporthe</i> sp. The absolute configurations of <b>1</b>–<b>5</b> were determined by low-temperature (100 K) single-crystal X-ray
diffraction with Cu Kα radiation. The compounds were evaluated
for cytotoxic activity; however, no compound showed significant cytotoxicity
against the tested cell lines at a concentration of 20 μM
P450-Modified Ribosomally Synthesized Peptides with Aromatic Cross-Links
Cyclization of linear peptides is an effective strategy
to convert flexible molecules into rigid compounds, which is of great
significance for enhancing the peptide stability and bioactivity.
Despite significant advances in the past few decades, Nature and chemists’
ability to macrocyclize linear peptides is still quite limited. P450
enzymes have been reported to catalyze macrocyclization of peptides
through cross-linkers between aromatic amino acids with only three
examples. Herein, we developed an efficient workflow for the identification
of P450-modified RiPPs in bacterial genomes, resulting in the discovery
of a large number of P450-modified RiPP gene clusters. Combined with
subsequent expression and structural characterization of the products,
we have identified 11 novel P450-modified RiPPs with different cross-linking
patterns from four distinct classes. Our results greatly expand the
structural diversity of P450-modified RiPPs and provide new insights
and enzymatic tools for the production of cyclic peptides
Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus <i>Diaporthe</i> sp.
A new sesquiterpenoid, diaporol A (<b>1</b>), possessing
a unique tricyclic lactone framework, eight new drimane sesquiterpenoids,
diaporols B–I (<b>2</b>–<b>9</b>), and the
known compounds <b>10</b> and <b>11</b> were isolated
from a culture of the mangrove-derived endophyte <i>Diaporthe</i> sp. The absolute configurations of <b>1</b>–<b>5</b> were determined by low-temperature (100 K) single-crystal X-ray
diffraction with Cu Kα radiation. The compounds were evaluated
for cytotoxic activity; however, no compound showed significant cytotoxicity
against the tested cell lines at a concentration of 20 μM