Dioxatricyclic and Oxabicyclic Polyketides from <i>Trichocladium opacum</i>

Five new polyketides, trichocladinols D–H (<b>1</b>–<b>5</b>) with dioxatricyclic (<b>1</b>–<b>3</b>) and oxabicyclic (<b>4</b> and <b>5</b>) skeletons, and the known massarilactone C (<b>6</b>) were isolated from the solid-substrate fermentation cultures of the ascomycete fungus <i>Trichocladium opacum</i>. The structures of <b>1</b>–<b>5</b> were determined mainly by NMR experiments, and <b>1</b>, <b>3</b>, and <b>4</b> were confirmed by X-ray crystallography. The absolute configurations of <b>1</b> and <b>3</b> were assigned by X-ray crystallography using Cu Kα radiation, whereas that of C-5 in <b>2</b> and <b>4</b> was deduced via the circular dichroism (CD) data. Compounds <b>2</b>–<b>4</b> showed weak cytotoxicity against the human tumor cell lines A549, HCT116, and SW480

Cytotoxic Cleistanthane and Cassane Diterpenoids from the Entomogenous Fungus <i>Paraconiothyrium hawaiiense</i>

Hawaiinolides A–D (<b>1</b>–<b>4</b>), four new secondary metabolites including three cleistanthane (<b>1</b>, <b>3</b>, and <b>4</b>) and one cassane (<b>2</b>) type of diterpene lactones, were isolated from the crude extract of <i>Paraconiothyrium hawaiiense</i>, a fungus entomogenous to the <i>Septobasidium</i>-infected insect <i>Diaspidiotus</i> sp. The structures of <b>1</b>–<b>4</b> were elucidated by nuclear magnetic resonance experiments, and <b>1</b> and <b>3</b> were further confirmed by X-ray crystallography. The absolute configuration of <b>1</b> was assigned via single-crystal X-ray diffraction analysis using Cu Kα radiation, whereas that of <b>2</b>–<b>4</b> was deduced via the circular dichroism data. Compound <b>1</b> showed significant cytotoxicity against a small panel of five human tumor cell lines, A549, T24, HeLa, HCT116, and MCF-7

Cytotoxic Cleistanthane and Cassane Diterpenoids from the Entomogenous Fungus <i>Paraconiothyrium hawaiiense</i>

Hawaiinolides A–D (<b>1</b>–<b>4</b>), four new secondary metabolites including three cleistanthane (<b>1</b>, <b>3</b>, and <b>4</b>) and one cassane (<b>2</b>) type of diterpene lactones, were isolated from the crude extract of <i>Paraconiothyrium hawaiiense</i>, a fungus entomogenous to the <i>Septobasidium</i>-infected insect <i>Diaspidiotus</i> sp. The structures of <b>1</b>–<b>4</b> were elucidated by nuclear magnetic resonance experiments, and <b>1</b> and <b>3</b> were further confirmed by X-ray crystallography. The absolute configuration of <b>1</b> was assigned via single-crystal X-ray diffraction analysis using Cu Kα radiation, whereas that of <b>2</b>–<b>4</b> was deduced via the circular dichroism data. Compound <b>1</b> showed significant cytotoxicity against a small panel of five human tumor cell lines, A549, T24, HeLa, HCT116, and MCF-7

A Spiro[chroman-3,7′-isochromene]-4,6′(8′<i>H</i>)-dione from the Cordyceps-Colonizing Fungus Fimetariella sp.

Fimetarone A (<b>1</b>), a metabolite with the new spiro[chroman-3,7′-isochromene]-4,6′(8′<i>H</i>)-dione skeleton, was isolated from cultures of the Cordyceps-colonizing fungus Fimetariella sp. Compound <b>1</b> was a 1:1 atropdiastereomeric mixture in NMR data, and a<i>S</i>,9<i>S</i> and a<i>R</i>,9<i>R</i> enantiomers were found and confirmed by X-ray crystallography. Compound <b>1</b> could be derived from the hypothetical precursors 3,4,5-trihydroxy-2-(2-methylene-3,5-dioxohexanoyl)benzoic acid (<b>5</b>) and lapidosin (<b>6</b>)

A Botryane Metabolite with a New Hexacyclic Skeleton from an Entomogenous Fungus <i>Hypocrea</i> sp.

Hypocrolide A (<b>1</b>), a botryane metabolite with a new hexacyclic skeleton, was isolated from cultures of the entomogenous fungus <i>Hypocrea</i> sp. The proposed structure was confirmed by X-ray crystallography using Cu Kα radiation. The mixed-biogenetic skeleton could be derived from the hypothetical precursors related to coumarin and dihydrobotrydiol, and the latter may be derived from the coisolated 10-oxodehydrodihydrobotrydial (<b>2</b>) or a similar analogue

Neonectrolide A, a New Oxaphenalenone Spiroketal from the Fungus <i>Neonectria</i> sp.

Neonectrolide A (<b>1</b>), an oxaphenalenone spiroketal with the previously undescribed (5,8′-dimethyl-5′-oxo-3a′,4,5,5′-tetrahydro-3<i>H</i>,3′<i>H</i>-spiro[furan-2,2′-isochromeno[3,4,5-<i>def</i>]chromene]-3′-yl)but-3-enoic acid skeleton, was isolated from cultures of the fungus <i>Neonectria</i> sp. Its absolute configuration was assigned by electronic circular dichroism (ECD) calculations. The skeleton of an oxaphenalenone fused with a 1,6-dioxaspiro[4.5]decane moiety in <b>1</b> could be derived from the coisolated putative precursors, corymbiferan lactone E (<b>2</b>) and 3-dehydroxy-4-<i>O</i>-acetylcephalosporolide C (<b>3</b>)

Identification of Oxaphenalenone Ketals from the Ascomycete Fungus <i>Neonectria</i> sp.

Neonectrolides B–E (<b>4</b>–<b>7</b>), four new oxaphenalenone ketals incorporating the new furo­[2,3-<i>b</i>]­isochromeno­[3,4,5-<i>def</i>]­chromen-11­(6a<i>H</i>)-one skeleton, were isolated from the fermentation extract of the ascomycete fungus <i>Neonectria</i> sp. in an in-depth investigation guided by HPLC fingerprint and a cytotoxicity assay. The previously identified oxaphenalenone spiroketal neonectrolide A (<b>1</b>) and its putative biosynthetic precursors (<b>2</b> and <b>3</b>) were also reisolated in the current work. The structures of <b>4</b>–<b>7</b> were primarily elucidated by interpretation of NMR spectroscopic data, and the absolute configurations were deduced by electronic circular dichroism calculations. Compound <b>6</b> showed cytotoxic effects against four of the six human tumor cell lines tested. Biosynthetically, compounds <b>4</b>–<b>7</b> could be derived via the Diels–Alder reaction cascades starting from derivatives of the co-isolated metabolites <b>2</b> and <b>3</b>

A Botryane Metabolite with a New Hexacyclic Skeleton from an Entomogenous Fungus <i>Hypocrea</i> sp.

Hypocrolide A (<b>1</b>), a botryane metabolite with a new hexacyclic skeleton, was isolated from cultures of the entomogenous fungus <i>Hypocrea</i> sp. The proposed structure was confirmed by X-ray crystallography using Cu Kα radiation. The mixed-biogenetic skeleton could be derived from the hypothetical precursors related to coumarin and dihydrobotrydiol, and the latter may be derived from the coisolated 10-oxodehydrodihydrobotrydial (<b>2</b>) or a similar analogue

The first 15 most abundant fungal OTUs in fresh leaf, raw and ripened Pu-erh samples.

<p>The first 15 most abundant fungal OTUs in fresh leaf, raw and ripened Pu-erh samples.</p

Genetic Manipulation of the Pneumocandin Biosynthetic Pathway for Generation of Analogues and Evaluation of Their Antifungal Activity

Pneumocandins are lipohexapeptides of the echinocandin family that potently interrupt fungal cell wall biogenesis by noncompetitive inhibition of 1,3-β-glucan synthase. The pneumocandin biosynthetic gene cluster was previously elucidated by whole genome sequencing. In addition to the core nonribosomal peptide synthetase and polyketide synthase (<i>GLNRPS4</i> and <i>GLPKS4</i>), the pneumocandin biosynthetic cluster includes two P450-type hemeprotein monooxygenase genes (<i>GLP450-1</i> and <i>GLP450-2</i>) and four nonheme mononuclear iron oxygenase genes (<i>GLOXY1</i>, <i>GLOXY2</i>, <i>GLOXY3</i>, and <i>GLOXY4</i>), which function to biosynthesize and create the unusual sequence of hydroxylated amino acids of the mature pneumocandin peptide. Insertional inactivation of three of these genes (<i>GLP450-1</i>, <i>GLP450-2</i>, and <i>GLOXY1</i>) generated 13 different pneumocandin analogues that lack one, two, three, or four hydroxyl groups on 4<i>R</i>,5<i>R</i>-dihydroxy-ornithine and 3<i>S</i>,4<i>S</i>-dihydroxy-homotyrosine of the parent hexapeptide. Among them, seven analogues are previously unreported genetically engineered pneumocandins whose structures were established by NMR experiments. These new pneumocandins afforded a unique opportunity for side-by-side exploration of the effects of hydroxylation on pneumocandin antifungal activity. All of these cyclic lipopeptides showed potent antifungal activities, and two new metabolites pneumocandins F (<b>3</b>) and G (<b>4</b>) were more potent <i>in vitro</i> against <i>Candida</i> species and <i>Aspergillus fumigatus</i> than the principal fermentation products, pneumocandins A₀ and B<sub>0.</sub