Pullenvalenes E-H: Triterpenyl-Aminoglycosides from an Australian Soil-Derived Fungus, sp.

Chemical profiling of soil-derived microbes collected under the auspices of the Australian citizen science initiative Soils for Science detected two fungi, sp. S4S-07771A07 and sp. S4S-14879B01, capable of producing pullenvalenes, a rare class of triterpene glycoside.

Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi.

A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of; (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and; (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs; to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of sp. CMB-F661 yielded the new regioisomeric chrysosporazine T () and U (), while precursor directed cultivation amplified production and yielded the very minor new natural products azachrysosporazine T1 () and U1 (), and the new unnatural analogues neochrysosporazine R () and S ().

Neochrysosporazines: Precursor-Directed Biosynthesis Defines a Marine-Derived Fungal Natural Product P-Glycoprotein Inhibitory Pharmacophore.

Upregulation of ATP binding cassette (ABC) transporter efflux pumps ( P-glycoprotein, P-gp) can impart multidrug resistance, rendering many chemotherapeutics ineffective and seriously limiting treatment regimes. While ABC transporters remain an attractive target for therapeutic intervention, the development of clinically useful small-molecule inhibitors has proved challenging. In this report, we describe the structure-activity relationship (SAR) analysis of a newly discovered P-gp inhibitory pharmacophore, phenylpropanoid piperazine chrysosporazines, produced by co-isolated marine-derived fungi.

Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, sp. CMB-F214.

Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, sp. CMB-F214, revealed the known chrysosporazines A-D (-) in addition to a suite of very minor analogues -. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of -; however, it did reveal that M2 agar cultivation produced the new natural product .