Marine-derived fungi are a significant source of pharmacologically active metabolites with interesting structural properties, especially terpenoids with biological and chemical diversity. In the past five years, there has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered. In this updated review, we examine the chemical structures and bioactive properties of new terpenes from marine-derived fungi, and the biodiversity of these fungi from 2015 to 2019. A total of 140 research papers describing 471 new terpenoids of six groups (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and meroterpenes) from 133 marine fungal strains belonging to 34 genera were included. Among them, sesquiterpenes, meroterpenes, and diterpenes comprise the largest proportions of terpenes, and the fungi genera of Penicillium, Aspergillus, and Trichoderma are the dominant producers of terpenoids. The majority of the marine-derived fungi are isolated from live marine matter: marine animals and aquatic plants (including mangrove plants and algae). Moreover, many terpenoids display various bioactivities, including cytotoxicity, antibacterial activity, lethal toxicity, anti-inflammatory activity, enzyme inhibitor activity, etc. In our opinion, the chemical diversity and biological activities of these novel terpenoids will provide medical and chemical researchers with a plenty variety of promising lead compounds for the development of marine drugs.

Tetramic acid (pyrrolidine-2,4-dione) compounds, isolated from a variety of marine and terrestrial organisms, have attracted considerable attention for their diverse, challenging structural complexity and promising bioactivities. In the past decade, marine-derived microorganisms have become great repositories of novel tetramic acids. Here, we discuss the biological activities of 277 tetramic acids of eight classifications (simple 3-acyl tetramic acids, 3-oligoenoyltetramic acids, 3-decalinoyltetramic acid, 3-spirotetramic acids, macrocyclic tetramic acids, N-acylated tetramic acids, α-cyclopiazonic acid-type tetramic acids, and other tetramic acids) from marine-derived microbes, including fungi, actinobacteria, bacteria, and cyanobacteria, as reported in 195 research studies up to 2019.

Previously unreported N,N′-ketal quinazolinone enantiomers [(−)-1 and (+)-1] and a new biogenetically related compound (2), along with six known compounds, 2-pyrovoylaminobenzamide (3), N-(2-hydroxypropanoyl)-2 amino benzoic acid amide (4), pseurotin A (5), niacinamide (6), citreohybridonol (7), citreohybridone C (8) were isolated from the ascidian-derived fungus Penicillium sp. 4829 in wheat solid-substrate medium culture. Their structures were elucidated by a combination of spectroscopic analyses (1D and 2D NMR and Electron Circular Dichroism data) and X-ray crystallography. The enantiomeric pair of 1 is the first example of naturally occurring N,N′-ketal quinazolinone possessing a unique tetracyclic system having 4-quinazolinone fused with tetrahydroisoquinoline moiety. The enantiomeric mixtures of 1 displayed an inhibitory effect on NO production in lipopolysaccharide-activated RAW264.7 cells, while the optically pure (–)-1 showed better inhibitory effect than (+)-1.

Culturing ascidian-derived fungus Amphichorda felina SYSU-MS7908 under standard laboratory conditions mainly yielded meroterpenoid, and nonribosomal peptide-type natural products. We sequenced the genome of Amphichorda felina SYSU-MS7908 and found 56 biosynthetic gene clusters (BGCs) after bioinformatics analysis, suggesting that the majority of those BGCSs are silent. Here we report our genome mining effort on one cryptic BGC by heterologous expression in Aspergillus oryzae NSAR1, and the identification of two new α-pyrone derivatives, amphichopyrone A (1) and B (2), along with a known compound, udagawanone A (3). Anti-inflammatory activities were performed, and amphichopyrone A (1) and B (2) displayed potent anti-inflammatory activity by inhibiting nitric oxide (NO) production in RAW264.7 cells with IC₅₀ values 18.09 ± 4.83 and 7.18 ± 0.93 μM, respectively.

There has been a tremendous increase in the rate of new terpenoids from marine-derived fungi being discovered, while new monoterpenes were rarely isolated from marine-derived fungi in the past two decades. Three new monoterpenes, diaporterpenes A–C (1–3), and one new α-pyrones, diaporpyrone A (6), along with nine known polyketides 4, 5, and 7–13 were isolated from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were elucidated based on extensive spectroscopic analyses (1D and 2D NMR and HR-ESIMS). The absolute configurations of 1 and 3 were identified by an X-ray crystallographic diffraction experiment using Cu-Ka radiation, and those of compound 2 were assigned by calculating NMR chemical shifts and ECD spectra. It afforded an example of natural epimers with different physical properties, especially crystallization, due to the difference in intermolecular hydrogen bonding. Compounds 9, 10, and 13 showed moderate total antioxidant capacity (0.82 of 9; 0.70 of 10; 0.48 of 13) with Trolox (total antioxidant capacity: 1.0) as a positive control, and compounds 5 and 7 showed anti-inflammatory activity with IC₅₀ values of 35.4 and 40.8 µM, respectively (positive control indomethacin: IC₅₀ = 35.8 µM).

Two new cembrane-type diterpenoids, lobophytins A (1) and B (3), and four new prostaglandins, (5E)-PGB₂ (10), (5E)-13,14-dihydro-PGB₂ (11), 13,14-dihydro-PGB₂ (12) and 13,14-dihydro-PGB₂-Me (13), together with ten known compounds were isolated from the soft coral Lobophytum sarcophytoides. The structures of these new secondary metabolites were identified by high resolution mass spectrometry (HR-ESIMS), nuclear magnetic resonance (NMR) and electron circular dichroism (ECD) analyses, as well as the modified Mosher’s method. Compounds 6, 7, 9, 10, 12, 13, 15 and 16 showed potential anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in RAW264.7 cells that were activated by lipopolysaccharide, with IC₅₀ values ranging from 7.1 to 32.1 μM and were better than the positive control indomethacin, IC₅₀ = 39.8 μM.