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).

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.

Fungal Duel between and Results in Dual Induction of Miktospiromide A and Kitrinomycin A.

Cocultivation of the fungi MST-FP1927 and MST-FP2004 resulted in the reciprocal induction of two new compounds, miktospiromide A () from . and kitrinomycin A () from . .

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 (-).

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.

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.

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.

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.

A Clade with Remarkable Biosynthetic Potential.

species produce a diverse range of biologically active compounds, including those biosynthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). Here, we report the biochemical and genomic analysis of sp. strain HM-SA03, isolated from the blue-ringed octopus, sp.

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.

Genome mining of a fungal endophyte of Taxus yunnanensis (Chinese yew) leads to the discovery of a novel azaphilone polyketide, lijiquinone.

Genome mining of Ascomycete sp. F53 (F53), a fungal endophyte of the traditional Chinese medicinal plant Taxus yunnanensis (Chinese yew), revealed 35 putative specialized metabolite biosynthesis gene clusters, one of which encodes a rarely seen tandem polyketide synthase pathway with close homology to azaphilone biosynthesis pathways. A novel compound, lijiquinone 1, was subsequently isolated from F53 and structurally and functionally characterized.

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, .

Chemical investigation of an undescribed Australian fungus, , led to the identification of the nanangenines - a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants.

Discovery, biosynthesis, and rational engineering of novel enterocin and wailupemycin polyketide analogues.

The marine actinomycete Streptomyces maritimus produces a structurally diverse set of unusual polyketide natural products including the major metabolite enterocin. Investigations of enterocin biosynthesis revealed that the unique carbon skeleton is derived from an aromatic polyketide pathway which is genetically coded by the 21.3 kb enc gene cluster in S.

Diversity and biosynthetic potential of culturable microbes associated with toxic marine animals.

Tetrodotoxin (TTX) is a neurotoxin that has been reported from taxonomically diverse organisms across 14 different phyla. The biogenic origin of tetrodotoxin is still disputed, however, TTX biosynthesis by host-associated bacteria has been reported. An investigation into the culturable microbial populations from the TTX-associated blue-ringed octopus Hapalochlaena sp.

Alternariol 9-O-methyl ether dimethyl sulfoxide monosolvate.

3,7-dihy-droxy-9-meth-oxy-1-methyl-6H-benzo[c]chromen-6-one dimethyl sulfoxide monosolvate), C15H12O5·C2H6OS, was isolated from an unidentified endophytic fungus (belonging to class Ascomycetes) of Taxus sp. In the crystal, both the alternariol 9-O-methyl ether (AME) and the dimethyl sulfoxide (DMSO) mol-ecules exhibit crystallographic mirror symmetry. One of the hy-droxy groups makes bifurcated hydrogen bonds, viz.

Unequivocal 13C NMR assignment of cyclohexadienyl rings in bromotyrosine-derived metabolites from marine sponges.

Bromotyrosine-derived compounds are commonly isolated from Verongida sponges and are a major class of marine natural products. Here we report on the unequivocal (13)C NMR assignment of the brominated carbons at positions C-2 and C-4 of the cyclohexadiene ring, two carbons whose resonances are often incorrectly assigned. Interpretation of HMBC data acquired for a series of known bromotyrosine analogues, which included ianthesine E(1), aerothionin (2), 11-hydroxyaerothionin (3), and 11,19-dideoxyfistularin-3 (4), allowed us to unequivocally assign the carbons in question, C-2 and C-4, through the observance of unique HMBC correlations from the C-1 hydroxyl proton.

On the origins and biosynthesis of tetrodotoxin.

The potent neurotoxin tetrodotoxin (TTX) has been identified from taxonomically diverse marine organisms. TTX possesses a unique cage-like structure, however, its biosynthesis has yet to be elucidated. Biosynthetic studies in the TTX-producing newt Taricha torosa, and in bacterial genera, including Vibrio, have proven inconclusive.

Policing starter unit selection of the enterocin type II polyketide synthase by the type II thioesterase EncL.

Enterocin is an atypical type II polyketide synthase (PKS) product from the marine actinomycete 'Streptomyces maritimus'. The enterocin biosynthesis gene cluster (enc) codes for proteins involved in the assembly and attachment of the rare benzoate primer that initiates polyketide assembly with the addition of seven malonate molecules and culminates in a Favorskii-like rearrangement of the linear poly-β-ketone to give its distinctive non-aromatic, caged core structure. Fundamental to enterocin biosynthesis, which utilizes a single acyl carrier protein (ACP), EncC, for both priming with benzoate and elongating with malonate, involves maintaining the correct balance of acyl-EncC substrates for efficient polyketide assembly.

Pestalactams A-C: novel caprolactams from the endophytic fungus Pestalotiopsis sp.

Chemical investigations of a fermentation culture from the endophytic fungus Pestalotiopsis sp. yielded three novel caprolactams, pestalactams A-C (). The structures of were determined by analysis of 1D and 2D-NMR, UV, IR, and MS data.