Five bergamotane sesquiterpenoid derivatives, brasilterpenes A–E (1–5), bearing an unreported spiral 6/4/5 tricyclic ring system, were isolated from the deep sea-derived ascomycete fungus Paraconiothyrium brasiliense HDN15-135. Their structures, including absolute configurations, were established by extensive spectroscopic methods complemented by single-crystal X-ray diffraction analyses, electronic circular dichroism (ECD), and density-functional theory (DFT) calculations of nuclear magnetic resonance (NMR) data including DP4+ analysis. The hypoglycemic activity of these compounds was assessed using a diabetic zebrafish model. Brasilterpenes A (1) and C (3) significantly reduced free blood glucose in hyperglycemic zebrafish in vivo by improving insulin sensitivity and suppressing gluconeogenesis. Moreover, the hypoglycemic activity of compound 3 was comparable to the positive control, anti-diabetes drug rosiglitazone. These results suggested brasilterpene C (3) had promising anti-diabetes potential.

Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.

Four new polyketides, namely furantides A–B (1–2), talamin E (3) and arugosinacid A (4), and two known polyketides were obtained from the mangrove-derived fungus Penicillium sp. HDN15-312 using the One Strain Many Compounds (OSMAC) strategy. Their chemical structures, including configurations, were elucidated by detailed analysis of extensive NMR spectra, HRESIMS and ECD. The DPPH radicals scavenging activity of 3, with an IC₅₀ value of 6.79 µM, was better than vitamin C.

α-Amylases, catalyzing starch degradation, serve as vital biocatalysts in industrial and pharmaceutical applications. This study identified a new α-amylase, Alphaz, from Nocardiopsis aegyptia HDN19-252 of Antarctic animal origin, achieving heterologous expression in Escherichia coli. Phylogenetic analysis confirmed its classification into the GH13_5 subfamily of glycoside hydrolases. Recombinant Alphaz exhibited optimal activity at 40 °C/pH 8.0 while maintaining stability across 0–30 °C and pH 6.6–9.6. Its distinctive halotolerant properties included full activity retention in 0.6 M NaCl and >60% efficiency in salt-free conditions. The enzyme exhibits tolerance to K⁺, Ca²⁺, and Fe³⁺ while demonstrating specific inhibition by Cu²⁺/Zn²⁺. With its heterologously validated functional properties, Alphaz emerges as a programmable enzymatic tool offering advantages in sustained-release formulation quality control, targeted prodrug modification, and precision medicine applications, thereby enabling sustainable biomanufacturing solutions that harmonize process reliability with environmental compatibility.

Ten new epipolythiodioxopiperazine (ETP) alkaloids, named corallomycetellains A–J (1–10), along with one known analogue, haematocin (11), were isolated from the fungi Corallomycetella repens HDN23-0007. Their structures, including absolute configurations, were established by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1–2 represent the first two examples of aranotin-type ETPs possessing an aromatic indole moiety. Compounds 2–4 all featured a unique C2-methyl disulfide substituent, whereas compound 4 additionally possessed a C2′-oxomethyl group. In in vitro cytotoxicity assays, compounds 7–10, which contained α–α′ polysulfide bridges, exhibited strong anticancer activity, with IC₅₀ values ranging from 1.1 to 9.3 μM.