Phenalenones and Polyesters from and Structure Revision of Talaromycesone A.

Investigation of the secondary metabolites of the filamentous fungus led to the isolation of two new phenalenone dimers, talarohemiketal A () and talaroazasone A (), and one new macrolide polyester, talaromacrolactone A (), along with the reported oxyphenalenone dimers talaromycesone A (), bacillisporin A (), bacillisporin B (), bacillisporin C (), -bacillisporin F (), and bacillisporin J (), the phenalenone monomer funalenone (), the polyesters 15G256α () and 15G256ν (), and 6-hydroxymellein (). Detailed analysis of 2D NMR correlations, supported by TDDFT calculations, led to the structural revision of talaromycesone A as from previously reported structure . In addition, the previously misassigned NMR spectra of compound have been corrected.

The aquastatin biosynthetic gene cluster encodes a versatile polyketide synthase capable of synthesising heteromeric depsides with diverse alkyl side chains.

Depsides have garnered substantial interest due to the diverse biological activities exhibited by members of this class. Among these are the antibacterial aquastatins, glycosylated heteromeric depsides formed through the condensation of orsellinic acid with corticiolic acid. In this work, we isolated aquastatins and the recently described geministatins, along with several novel aquastatin-related depsides with different alkyl side chains from the fungus MST-FP2131.

Geministatins: new depside antibiotics from the fungus Austroacremonium gemini.

Two new depside antibiotics, geministatins A (1) and B (2), were isolated from the fungus Austroacremonium gemini MST-FP2131 (Sordariomycetes, Ascomycota), which was recovered from rotting wood in the wet tropics of northern Australia. The structures of the geministatins were elucidated by detailed spectroscopic analysis, chemical degradation and comparison with literature values. Chemical degradation of 1 and 2 yielded three new analogues, geministatins C-E (3-5), as well as a previously reported compound dehydromerulinic acid A (6).

Discovery and heterologous biosynthesis of glycosylated polyketide luteodienoside A reveals unprecedented glucinol-mediated product offloading by a fungal carnitine -acyltransferase domain.

Luteodienoside A is a novel glycosylated polyketide produced by the Australian fungus MST-FP2246, consisting of an unusual 1--β-d-glucopyranosyl--inositol (glucinol) ester of 3-hydroxy-2,2,4-trimethylocta-4,6-dienoic acid. Mining the genome of identified a putative gene cluster for luteodienoside A biosynthesis (), harbouring a highly reducing polyketide synthase (HR-PKS, LtbA) fused at its C-terminus to a carnitine -acyltransferase (cAT) domain. Heterologous pathway reconstitution in , substrate feeding assays and gene truncation confirmed the identity of the cluster and demonstrated that the cAT domain is essential for offloading luteodienoside A from the upstream HR-PKS.

Heterologous Biosynthesis of the Sterol -Acyltransferase Inhibitor Helvamide Unveils an α-Ketoglutarate-Dependent Cross-Linking Oxygenase.

We have identified the biosynthetic gene cluster () for the sterol -acyltransferase inhibitor helvamide () from the genome of MST-FP2007. Heterologous expression of in produced a previously unreported analog helvamide B (). An α-ketoglutarate-dependent oxygenase Hvm1 was shown to catalyze intramolecular cyclization of to yield .

Talcarpones A and B: bisnaphthazarin-derived metabolites from the Australian fungus Talaromyces johnpittii sp. nov. MST-FP2594.

Talcarpones A (1) and B (2) are rare bisnaphthazarin derivatives produced by Talaromyces johnpittii (ex-type strain MST-FP2594), a newly discovered Australian fungus, which is formally described and named herein. The talcarpones were isolated along with the previously reported monomeric naphthoquinone, aureoquinone (3), suggesting a biosynthetic link between these metabolites. Talcarpone A is a lower homologue of hybocarpone (4), which was first isolated from a mycobiont of the lichen Lecanora hybocarpa.

Turonicin A, an Antifungal Linear Polyene Polyketide from an Australian sp.

Turonicin A () was isolated from sp. MST-123921, which was recovered from soil collected on the banks of the Turon River in New South Wales, Australia. Turonicin A () is an amphoteric linear polyene polyketide featuring independent pentaene and tetraenone chromophores and is structurally related to linearmycins A-C (-).

Dendrillic Acids A and B: Nitrogenous, Rearranged Spongian Nor-Diterpenes from a sp. Marine Sponge.

Two nitrogenous rearranged spongian nor-diterpenoids, dendrillic acids A and B, were isolated from a marine sponge sp. (order: Dendroceratida; family: Darwinellidae). The structures of the metabolites were elucidated on the basis of spectroscopic analysis as well as density functional theory prediction of NMR chemical shifts and application of the DP4+ algorithm.

Synthesis, Characterization, and Bioactivity of the Lichen Pigments Pulvinamide, Rhizocarpic Acid, and Epanorin and Congeners.

The lichen natural products pulvinamide, rhizocarpic acid, and epanorin have been synthesized and characterized spectroscopically and by X-ray crystallography. The syntheses, by ring-opening of pulvinic acid dilactone (PAD), may well be biomimetic, given the well-known occurrence of PAD in lichen. The enantiomers, -rhizocarpic acid and -epanorin, and corresponding carboxylic acids, norrhizocarpic acid and norepanorin, were similarly prepared.

Resorculins: hybrid polyketide macrolides from sp. MST-91080.

Fourteen-membered macrolides are a class of compounds with significant clinical value as antibacterial agents. As part of our ongoing investigation into the metabolites of sp. MST-91080, we report the discovery of resorculins A and B, unprecedented 3,5-dihydroxybenzoic acid (α-resorcylic acid)-containing 14-membered macrolides.

Type-I Hemins and Free Porphyrins from a Western Australian Sponge sp.

Two novel free porphyrins, isabellins A and B, as well as the known compounds corallistin D and deuteroporphyrin IX were isolated from a marine sponge sp. LC-MS analysis of the crude extract revealed that the natural products were present both as free porphyrins and iron(III) coordinated hemins, designated isabellihemin A, isabellihemin B, corallistihemin D and deuterohemin IX, respectively. Structures were determined via high-resolution mass spectrometry, UV-Vis spectroscopy and extensive NOESY NMR spectroscopic experiments.

Fuligopyrones from the Fruiting Bodies of Myxomycete Offer Short-Term Protection from Abiotic Stress Induced by UV Radiation.

The myxomycete , colloquially referred to as "dog vomit fungus", forms vibrant yellow fruiting bodies (aethalia) on wood chips during warm and humid conditions in spring. In 2018, ideal climatic conditions in Sydney, Australia, provided a rare opportunity to access abundant quantities of aethalia, which enabled the isolation, purification, structure elucidation, and biological screening of two avenalumamide pyrones, fuligopyrone () and fuligopyrone B (). While and did not exhibit any appreciable biological activity, their significant UV absorption at 325 nm suggested they may be acting as transient sunscreens to help protect the fruiting mass from exposure to sunlight.

Suertides A-C: selective antibacterial cyclic hexapeptides from Amycolatopsis sp. MST-135876v3.

Amycolatopsis sp. MST-135876 was isolated from soil collected from the riverbank of El Pont de Suert, Catalonia, Spain. Cultivation of MST-135876 on a range of media led to the discovery of a previously unreported dichlorinated cyclic hexapeptide, suertide A (D-Ser, 5-Cl-D-Trp, 6-Cl-D-Trp, L-Ile, D-Val, D-Glu), featuring an unprecedented pair of adjacent 5/6-chlorotryptophan residues.

Discovery of brevijanazines from reveals the molecular basis for -nitrobenzoic acid in fungi.

The brevijanazines are novel -nitrobenzoylated piperazines isolated from . Their structures were elucidated by spectroscopic analysis, X-ray crystallography and total synthesis. Heterologous biosynthesis, precursor feeding and microsomal assays unveiled the biosynthetic pathway to the brevijanazines, featuring a cytochrome P450 oxygenase that converts -aminobenzoic acid to -nitrobenzoic acid.

Yeppoonic acids A - D: 1,2,4-trisubstituted arene carboxylic acid co-metabolites of conglobatin from an Australian Streptomyces sp.

Streptomyces sp. MST-91080 was isolated from a soil sample collected in Queensland, Australia. From this strain, yeppoonic acids A - D were purified and spectroscopically characterised.

Genome Mining of Unearths Cryptic Polyketide Hancockinone A Featuring a Prenylated 6/6/6/5 Carbocyclic Skeleton.

Activation of a cryptic polyketide synthase gene cluster from via overexpression of the gene-cluster-specific transcription factor HknR led to the discovery of a novel polycyclic metabolite, which we named hancockinone A. The compound features an unprecedented prenylated 6/6/6/5 tetracarbocyclic skeleton and shows moderate antibacterial activity. Heterologous expression, substrate feeding, and in vitro assays confirmed the role of cytochrome P450 HknE in constructing the five-membered ring in hancockinone A from the precursor neosartoricin B.

Characterisation and heterologous biosynthesis of burnettiene A, a new polyene-decalin polyketide from .

Chemical exploration of the recently described Australian fungus, , uncovered a new metabolite, burnettiene A. Here, we characterise the structure of burnettiene A as a polyene-decalin polyketide. Bioinformatic analysis of the genome of identified a putative biosynthetic gene cluster for burnettiene A (), consisting of eight genes and sharing similarity to the fusarielin gene cluster.

Testing the effectiveness of community-engaged citizen science to promote physical activity, foster healthier neighborhood environments, and advance health equity in vulnerable communities: The Steps for Change randomized controlled trial design and methods.

While low-income midlife and older adults are disproportionately affected by non-communicable diseases that can be alleviated by regular physical activity, few physical activity programs have been developed specifically with their needs in mind. Those programs that are available typically do not address the recognized local environmental factors that can impact physical activity. The specific aim of the Steps for Change cluster-randomized controlled trial is to compare systematically the initial (one-year) and sustained (two-year) multi-level impacts of an evidence-based person-level physical activity intervention (Active Living Every Day [ALED] and age-relevant health education information), versus the ALED program in combination with a novel neighborhood-level citizen science intervention called Our Voice.

Evaluation of Benzguinols as Next-Generation Antibiotics for the Treatment of Multidrug-Resistant Bacterial Infections.

Our recent focus on the "lost antibiotic" unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against isolates either susceptible or resistant to methicillin. Here, we show further activity of the benzguinols against methicillin-resistant isolates of the animal pathogen , with minimum inhibitory concentration (MIC) ranging 0.5-1 μg/mL.

Chlorinated metabolites from Streptomyces sp. highlight the role of biosynthetic mosaics and superclusters in the evolution of chemical diversity.

LCMS-guided screening of a library of biosynthetically talented bacteria and fungi identified Streptomyces sp. MST- as a prolific producer of chlorinated metabolites. We isolated and characterised six new and nine reported compounds from MST-, belonging to three discrete classes - the depsipeptide svetamycins, the indolocarbazole borregomycins and the aromatic polyketide anthrabenzoxocinones.

Production of novel pladienolide analogues through native expression of a pathway-specific activator.

Aberrant splicing of pre-mRNA is implicated in many human genetic disorders. Small molecules that target the spliceosome are important leads as therapeutics and research tools, and one compound of significant interest is the polyketide natural product pladienolide B. Here, we describe the reactivation of quiescent pladienolide B production in the domesticated lab strain AS6200 by overexpression of the pathway-specific activator PldR.

TriTOX: A novel Trichomonas vaginalis assay platform for high-throughput screening of compound libraries.

Trichomonas vaginalis is a neglected urogenital parasitic protist that causes 170 million cases of trichomoniasis annually, making it the most prevalent non-viral, sexually transmitted disease. Trichomoniasis treatment relies on nitroheterocyclics, such as metronidazole. However, with increasing drug-resistance, there is an urgent need for novel anti-trichomonals.

Semisynthesis and biological evaluation of a focused library of unguinol derivatives as next-generation antibiotics.

In this study, we report the semisynthesis and in vitro biological evaluation of thirty-four derivatives of the fungal depsidone antibiotic, unguinol. Initially, the semisynthetic modifications were focused on the two free hydroxy groups (3-OH and 8-OH), the three free aromatic positions (C-2, C-4 and C-7), the butenyl side chain and the depsidone ester linkage. Fifteen first-generation unguinol analogues were synthesised and screened against a panel of bacteria, fungi and mammalian cells to formulate a basic structure activity relationship (SAR) for the unguinol pharmacophore.

Total Synthesis of the Antitumor-Antitubercular 2,6'-Bijuglone Natural Product Diospyrin and Its 3,6'-Isomer.

The 2,6'-bijuglone natural product diospyrin and its unnatural 3,6'-isomer idospyrin have been synthesized in seven steps each from ,-diethylsenecioamide in overall yields of 12% and 13%, respectively. The syntheses diverge from ramentaceone (7-methyljuglone) and include a key Suzuki-Miyaura cross-coupling. Diospyrin, idospyrin, and several synthetic precursors exhibit potent and selective cytotoxicity to the murine myeloma NS-1 cell line over neonatal foreskin cells.

Hancockiamides: phenylpropanoid piperazines from are biosynthesised by a versatile dual single-module NRPS pathway.

The hancockiamides are an unusual new family of N-cinnamoylated piperazines from the Australian soil fungus Aspergillus hancockii. Genomic analyses of A. hancockii identified a biosynthetic gene cluster (hkm) of 12 genes, including two single-module nonribosomal peptide synthetase (NRPS) genes.