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Subjecting the Australian marine-derived fungus Aspergillus noonimiae 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 ( 1 - 3 ), along with the known analogue coelomycin ( 4 ), as well as a new azaphilone, noonaphilone A ( 5 ). Structures were assigned to 1 - 5 on the basis of a detailed spectroscopic analysis, and in the case of 1 - 2 , an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for 1 - 4 , involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, 2 incorporates a rare meta -Tyr motif, typically only reported in a limited array of Streptomyces metabolites. Similarly, a plausible biosynthetic pathway is proposed for 5 , highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7 R noonaphilone A ( 5 ) versus the 7 S deflectin 1a ( 6 ).

An integrated program of chemical profiling (GNPS) coupled with an expanded format 24-well-plate miniaturized cultivation profiling (MATRIX) utilizing traditional as well as grain/pulse and cereal media permitted rapid prioritization of Aspergillus terreus CMB-SWF012 as a source of unprecedented natural products. Scaled-up cultivation on rice and PDA yielded the rare tripeptides asterripeptides A-C ( 1 - 3 ), new indolo-sesquiterpene Michael adducts terreusides A and B ( 4 and 5 ), and known precursors asterresin A ( 6 ) and (+)-giluterrin ( 7 ). Structures for 1 - 7 were assigned by detailed spectroscopic and chemical analysis and biosynthetic considerations.

While investigating the cytotoxic activity of the methanol extract of an Australian marine sponge Stelletta sp. (Demospongiae), a new diketopiperazine, cyclo-(4-S-hydroxy-R-proline-R-isoleucine) (1), was isolated together with the known bengamides; A (2), F (3), N (4), Y (5), and bengazoles; Z (6), C(4) (7) and C(6) (8). The isolation and structure elucidation of the diketopiperazine (1), together with the activity of 1-8 against a panel of human and mammalian cell lines are discussed.