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Utilizing a gene evolution-oriented approach for gene cluster mining, a cryptic cytochalasin-like gene cluster ( sla ) in Antarctic-derived Simplicillium lamelliciola HDN13430 was identified. Compared with the canonical cytochalasin biosynthetic gene clusters (BGCs), the sla gene cluster lacks the key α,β-hydrolase gene. Heterologous expression of the sla gene cluster led to the discovery of a new compound, slamysin ( 1 ), characterized by an N -acylated amino acid structure and demonstrating weak anti- Bacillus cereus activity. These findings underscore the potential of genetic evolution in uncovering novel compounds and indicating specific adaptive evolution within specialized habitats.

Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A-F ( 1 - 6 ), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D-F ( 4 - 6 ) possess unique backbones bearing a tetrahydropyridoindoles unit, which make them the first examples discovered in naturally occurring peptides. The absolute configurations of structures were unambiguously determined using solid-phase total synthesis assisted by Marfey's method, and all compounds were evaluated for their inhibition of human (h) nicotinic acetylcholine receptor subtypes. Compound 2 showed significant inhibitory activity. A preliminary structure-activity relationship investigation revealed that the tryptophan residue and the C-terminal with methoxy group were important to the inhibitory activity. Further, the high binding affinity of compound 2 to h α 4 β 2 was explained by molecular docking studies.

The Wnt/β-catenin signaling pathway is an evolutionarily conserved signaling cascade involved in a broad range of biological roles. Dysregulation of the Wnt/β-catenin pathway is implicated in congenital malformations and various kinds of cancers. We discovered a novel Wnt/β-catenin inhibitor, talaverrucin A ( 1 ), featuring an unprecedented 6/6/6/5/5/5/6 fused ring system, from an Antarctica sponge-derived fungus Talaromyces sp. HDN151403. Talaverrucin A exhibits inhibitory activity on the Wnt/β-catenin pathway in both zebrafish embryos in vivo and cultured mammalian cells in vitro , providing a naturally inspired small molecule therapeutic lead to target the Wnt/β-catenin pathway.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases of the pancreas with fatal proliferation and metastasis and no medicine available for treatment. From an Antarctica sponge-derived fungus, Aspergillus insulicola HDN151418, four new nitrobenzoyl sesquiterpenoids, namely, insulicolides D-G ( 1 - 4 ), were isolated. Compounds 3 and 4 exhibited selective inhibition against human PDAC cell lines. Further studies indicated that compound 4 could significantly suppress cell proliferation to induce apoptosis and blocked migration and invasion of PDAC cells. Compound 4 could also avoid resistance and improved the therapeutic effect of the chemotherapy drug gemcitabine. A preliminary mechanism study showed that compound 4 can significantly inhibit the expression of EGFR and XIAP in PDAC cells. Altogether, 4 is a potential lead compound for anti-PDAC drug research.

Six new nonadride derivatives, named talarodrides A-F ( 1 - 6 ), were isolated from the Antarctic sponge-derived fungus Talaromyces sp. HDN1820200. All structures including the absolute configurations were deduced by extensive spectroscopic analysis and computational ECD calculations. Compounds 1 - 4 share a rare caged bicyclo[4.3.1]-deca-1,6-diene with a bridgehead olefin and maleic anhydride core skeleton, while compounds 5 and 6 possess the first case of a naturally occurring 5/7/6 methanocyclonona[ c ]furan skeleton. Talarodride A ( 1 ) and talarodride B ( 2 ) showed selective inhibitory effects against Proteus mirabilis and Vibrio parahemolyticus with MICs of 3.13-12.5 μM.

Four new anthraquinone derivatives, namely saliniquinones G-I ( 1 - 3 ) and heraclemycin E ( 4 ), were obtained from the Antarctic marine-derived actinomycete Nocardiopsis aegyptia HDN19-252, guided by the Global Natural Products Social (GNPS) molecular networking platform. Their structures, including absolute configurations, were elucidated by extensive NMR, MS, and ECD analyses. Compounds 1 and 2 showed promising inhibitory activity against six tested bacterial strains, including methicillin-resistant coagulase-negative staphylococci (MRCNS), with MIC values ranging from 3.1 to 12.5 μM.

Three new aspochracin-type cyclic tripeptides, sclerotiotides M-O ( 1 - 3 ), together with three known analogues, sclerotiotide L ( 4 ), sclerotiotide F ( 5 ), and sclerotiotide B ( 6 ), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus , Proteus species , Mycobacterium phlei , Bacillus subtilis , Vibrio parahemolyticus , Edwardsiella tarda , MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM.

Three new polyketides, ketidocillinones A-C ( 1 - 3 ), were discovered from the extract of an Antarctica sponge-derived fungus Penicillium sp. HDN151272. All the structures were deduced by spectroscopic data, including NMR and HRESIMS. The absolute configuration of compound 3 was established by using ECD calculation. Compounds 1 - 3 can be slowly oxidized to quinone form when exposed to air. Ketidocillinones B and C ( 2 and 3 ) exhibited potent antibacterial activity against Pseudomonas aeurigenosa , Mycobacterium phlei, and MRCNS (methicillin-resistant coagulase-negative staphylococci ) with MIC values ranging from 1.56 to 25.00 µg/mL., Competing Interests: The authors declare no conflict of interest.

Two new meroterpenoids, named chrodrimanins I and J (1 and 2), together with five known biosynthetically related chrodrimanins (3-7), were isolated from the culture of the Antarctic moss-derived fungus Penicillium funiculosum GWT2-24. Distinguished from all of the reported chrodrimanins, compounds 1 and 2 possess a unique cyclohexanone (E ring) instead of a δ-lactone ring. These structures including the absolute configurations were established on the basis of MS, NMR, and X-ray crystallographic analysis. Compounds 1-7 showed no cytotoxic or antibacterial activities, while the known compounds 3, 5, and 6 exhibited inhibitory activities against influenza virus A (H1N1), with IC50 values ranged from 21 to 57 μM.

Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp. PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1–5 and a new rare lactam-type eremophilane 6, together with three known compounds 7–9. The structures of these diverse sesquiterpenes were determined by extensive NMR and mass spectroscopic analyses. Compounds 1, 2, 4–6, 8 and 9 were evaluated for their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the most active one with IC50 value of 5.2 lM against the A-549 cells.

A new chloro-trinoreremophilane sesquiterpene 1, three new chlorinated eremophilane sesquiterpenes 2-4, together with a known compound, eremofortine C (5), were isolated from an Antarctic deep-sea derived fungus, Penicillium sp. PR19N-1. Structures were established using IR, HRMS, 1D and 2D NMR techniques. In addition, the plausible metabolic network of these isolated products is proposed. Compound 1 showed moderate cytotoxic activity against HL-60 and A549 cancer cell lines.

Two new epipolythiodioxopiperazines, named chetracins B and C (1 and 2), and five new diketopiperazines, named chetracin D (4) and oidioperazines A-D (5, 10, 12, and 13), were isolated from the fungus Oidiodendron truncatum GW3-13, along with six known compounds (3, 6, 7, 8, 9, and 11). Their structures were elucidated by extensive NMR, MS, and CD analyses, as well as chemical transformation. An in vitro MTT cytotoxicity assay revealed potent biological activity for 1 in the nanomolar range against a panel of five human cancer lines.