Miniaturized Cultivation Profiling (MATRIX)-Facilitated Discovery of Noonazines A-C and Noonaphilone A from an Australian Marine-Derived Fungus, CMB-M0339.

Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (-), along with the known analogue coelomycin (), as well as a new azaphilone, noonaphilone A (). Structures were assigned to - on the basis of a detailed spectroscopic analysis, and in the case of -, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for -, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor.

Tepuazines A-E: Phenazine Glycosides from a Venezuelan Quartz-Rich (Tepui) Cave Soil-Derived CMB-CA091.

Investigation of the secondary metabolites of CMB-CA091 isolated from the quartz-rich (tepui) soil of a cave in Venezuela yielded two new dimeric phenazine glycosides, tepuazines A and B ( and ); three new monomeric phenazine glycosides, tepuazines C-E (-); and a series of known analogues, baraphenazine G (), phenazinolin D (), izumiphenazine C (), 4-methylaminobenzoyl-l-rhamnopyranoside (), and 2-acetamidophenol (). Structures were assigned to - on the basis of detailed spectroscopic analysis and biosynthetic considerations, with and featuring a rare 2-oxabicyclo[3.3.

Noonindoles G-L: Indole Diterpene Glycosides from the Australian Marine-Derived Fungus CMB-M0339.

Fungal indole diterpenes (IDTs) occupy a valuable region of bioactive natural product chemical space, displaying potent and selective inhibition of therapeutically important ion channels and with potential application in the treatment of glaucoma, cancer, and neurodegenerative diseases, as well as insecticides and antivirals. We have employed an integrated workflow of analytical scale chemical profiling using GNPS (Global Natural Products Social molecular networking) and cultivation profiling (also known as "MATRIX" miniaturized microbioreactor) to detect, prioritize, optimize the production, isolate, characterize, and identify a new series of indole diterpenes, noonindoles G-L (-), from an Australian marine-derived fungus, CMB-M0339. The first reported examples of IDT glycosides, the molecular structures for -, were assigned on the basis of detailed spectroscopic analysis and biosynthetic considerations.

Noonindoles A-F: Rare Indole Diterpene Amino Acid Conjugates from a Marine-Derived Fungus, CMB-M0339.

Analytical scale chemical/cultivation profiling prioritized the Australian marine-derived fungus CMB-M0339. Subsequent investigation permitted isolation of noonindoles A-F (-) and detection of eight minor analogues (-) as new examples of a rare class of indole diterpene (IDT) amino acid conjugate, indicative of an acyl amino acid transferase capable of incorporating a diverse range of amino acid residues. Structures for - were assigned by detailed spectroscopic and X-ray crystallographic analysis.

Structure Revision of Penipacids A-E Reveals a Putative New Cryptic Natural Product, -aminoanthranilic Acid, with Potential as a Transcriptional Regulator of Silent Secondary Metabolism.

Reconsideration of the spectroscopic data for penipacids A-E, first reported in 2013 as the acyclic amidines - from the South China deep sea sediment-derived fungus SD-44, prompted a total synthesis structure revision as the hydrazones -. This revision strongly supported the proposition that penipacids A-B (-) were artifact Schiff base adducts of the cryptic (undetected) natural product -aminoanthranilic acid () with diacetone alcohol, induced by excessive exposure to acetone and methanol under acidic handling conditions. Likewise, the revised structures for penipacids C-D (-) and E () raise the possibility that they may also be artifact Schiff base adducts of and the media constituents pyruvic acid and furfural, respectively.