Fungal nonribosomal peptides (NRPs) and the related polyketide–nonribosomal peptide hybrid products (PK–NRPs) are a prolific source of bioactive compounds, some of which have been developed into essential drugs.

Three new prenylated indole 2,5-diketopiperazine alkaloids (1–3) with nine known ones (5–13), one new indole alkaloid (4), and one new bis-benzyl pyrimidine derivative (14) were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC₅₀ values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.

Conserved biosynthetic gene clusters (BGCs) are often tied to the production of natural products that perform critical functions in an organism's physiology and ecological interactions. Here, by phylogenetic analysis across the bacterial genus, we report the obligate conservation of a BGC in genomes of cosmopolitan marine Microbulbifer bacteria. This genus is a common member of marine microbiomes, and this BGC was conserved in Microbulbifer genomes regardless of phylogenetic or geographical dispersal. The post-translationally modified peptidic product encoded by this BGC─which was accessed via heterologous production and its structure elucidated using a combination of mass spectrometry and NMR spectroscopy─was found to be a copper chelator. Similar BGCs were then found in genomes of other marine bacterial genera coinhabiting the microbiomes of sponges and corals. The phylogenomic workflows described herein were implemented in a pedagogic setting at the Georgia Institute of Technology to provide hands-on instruction to undergraduate students in bacterial phylogeny, genome mining, and natural product chemistry.