Phoma spp. an untapped treasure of cytotoxic compounds: current status and perspectives.

The genus Phoma has been explored for a wide range of secondary metabolites signifying a huge range of bioactivities. Phoma sensu lato is a major group that secretes several secondary metabolites. The genus Phoma mainly includes Phoma macrostoma, P. multirostrata, P. exigua, P. herbarum, P. betae, P. bellidis, P. medicaginis, P. tropica, and many more species from the genus that are continuously being identified for their potential secondary metabolites. The metabolite spectrum includes bioactive compounds like phomenon, phomin, phomodione, cytochalasins, cercosporamide, phomazines, and phomapyrone reported from various Phoma spp. These secondary metabolites show a broad range of activities including antimicrobial, antiviral, antinematode, and anticancer. The present review is aimed to emphasize the importance of Phoma sensu lato fungi, as a natural source of biologically active secondary metabolites, and their cytotoxic activities. So far, cytotoxic activities of Phoma spp. have not been reviewed; hence, this review will be novel and useful for the readers to develop Phoma-derived anticancer agents. KEY POINTS: • Different Phoma spp. contain a wide variety of bioactive metabolites. • These Phoma spp. also secrete cytotoxic and antitumor compounds. • The secondary metabolites can be used for the development of anticancer agents.

A strain of Phoma species improves drought tolerance of Pinus tabulaeformis.

Global warming has led to frequent droughts, posing challenges for afforestation in arid and semiarid regions. In search of labor-saving and money-saving methods to improve the survival and growth rates of trees in these regions, we isolated and identified fungal endophytes that can potentially enhance the drought-resistance abilities of seedlings. We isolated 93 endophytic strains from the roots of Pinus tabulaeformis trees grown on an arid cliff. Three isolates increased the drought resistance of the tree seedlings. Using morphological, molecular, and physiological-biochemical methods, we identified three isolates as different clones of a strain of Phoma spp. and studied the strain's effect on stress resistance-related substances in the seedlings. The results showed that the strain improved drought tolerance and increased the seedlings' proline levels and antioxidant enzyme activities. The strain also secreted abundant extracellular abscisic acid, which likely triggered the seedlings' protective mechanisms. This endophytic strain may provide a cheaper labor-saving, sustainable alternative to traditional methods of enhancing drought resistance.

Macrooxazoles A-D, New 2,5-Disubstituted Oxazole-4-Carboxylic Acid Derivatives from the Plant Pathogenic Fungus Phoma macrostoma.

In our ongoing search for new bioactive fungal metabolites, four previously undescribed oxazole carboxylic acid derivatives (1-4) for which we proposed the trivial names macrooxazoles A-D together with two known tetramic acids (5-6) were isolated from the plant pathogenic fungus Phoma macrostoma. Their structures were elucidated based on high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The hitherto unclear structure of macrocidin Z (6) was also confirmed by its first total synthesis. The isolated compounds were evaluated for their antimicrobial activities against a panel of bacteria and fungi. Cytotoxic and anti-biofilm activities of the isolates are also reported herein. The new compound 3 exhibited weak-to-moderate antimicrobial activity as well as the known macrocidins 5 and 6. Only the mixture of compounds 2 and 4 (ratio 1:2) showed weak cytotoxic activity against the tested cancer cell lines with an IC50 of 23 µg/mL. Moreover, the new compounds 2 and 3, as well as the known compounds 5 and 6, interfered with the biofilm formation of Staphylococcus aureus, inhibiting 65%, 75%, 79%, and 76% of biofilm at 250 µg/mL, respectively. Compounds 5 and 6 also exhibited moderate activity against S. aureus preformed biofilm with the highest inhibition percentage of 75% and 73% at 250 µg/mL, respectively.

Cytochalasins from an endophytic fungus Phoma multirostrata XJ-2-1 with cell cycle arrest and TRAIL-resistance-overcoming activities.

Nine new (1-9) and four known (10-13) [13]cytochalasins, along with three known 24-oxa[14]cytochalasins (14-16), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the fibrous root of Parasenecio albus. Their structures were elucidated by interpretation of the nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations were assigned by single-crystal X-ray crystallography, modified Mosher's method, and by analysis of their experimental electronic circular dichroism (ECD) spectra. Compound 6 could induce cell cycle arrest at G2-phase in CT26 and A549 cells, and displayed moderate cytotoxicity against CT26 and A549 cell lines with IC50 values of 6.03 and 5.04 µM, respectively. Co-treatment of 7-9, 13 and 16 with tumor necrosis factor related apoptosis inducing ligand (TRAIL) could significantly decrease the cell viability of A549, which revealed that cytochalasins could possibly be a new group of TRAIL sensitizers in lung cancer therapy.

Fungal transformation of selenium and tellurium located in a volcanogenic sulfide deposit.

Microbial reduction of soluble selenium (Se) or tellurium (Te) species results in immobilization as elemental forms and this process has been employed in soil bioremediation. However, little is known of direct and indirect fungal interactions with Se-/Te-bearing ores. In this research, the ability of Phoma glomerata to effect transformation of selenite and tellurite was investigated including interaction with Se and Te present in sulfide ores from the Kisgruva Proterozoic volcanogenic deposit. Phoma glomerata could precipitate elemental Se and Te as nanoparticles, intracellularly and extracellularly, when grown with selenite or tellurite. The nanoparticles possessed various surface capping molecules, with formation being influenced by extracellular polymeric substances. The presence of sulfide ore also affected the production of exopolysaccharide and protein. Although differences were undetectable in gross Se and Te ore levels before and after fungal interaction using X-ray fluorescence, laser ablation inductively coupled plasma mass spectrometry of polished flat ore surfaces revealed that P. glomerata could effect changes in Se/Te distribution and concentration indicating Se/Te enrichment in the biomass. These findings provide further understanding of fungal roles in metalloid transformations and are relevant to the geomicrobiology of environmental metalloid cycling as well as informing applied approaches for Se and Te immobilization, biorecovery or bioremediation.