The endophytic fungus Aspergillus is considered as an enormous source of chemical leads with promising biological activities. Different Aspergillus species have proved their ability to produce plenty of secondary metabolites including butenolides, alkaloids, terpenoids, cytochalasins, phenalenones, ρ-terphenyls, xanthones, sterols, diphenyl ether and anthraquinone derivatives with diverse biological activities, such as anti-cancer, antifungal, anti-bacterial, anti-viral, anti-inflammatory, antitrypanosomal and antileishmanial activities. From January 2015 until December 2019, three hundred and sixty-one secondary metabolites were reported from different endophytic Aspergillus species. This review discusses the isolated secondary metabolites from different endophytic Aspergillus species reported from January 2015 to December 2019 along with their reported biological activities and structural aspects whenever applicable.

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Natural product diversity from the endophytic fungi of the genus Aspergillus

Microalgae are a promising biomass feedstock for biofuels production. The use of wastewater effluent as a nutrient medium would improve the economics of microalgal biofuels production. Bacterial communities in aquatic environments may either stimulate or inhibit microalgal growth. Microalgal productivity could be enhanced if the positive effects of indigenous bacteria could be exploited. However, much is unknown about the effects of indigenous bacteria on microalgal growth and the characteristics of bacterial communities associated with microalgae in microalgae–effluent culture. To assess the effects of the indigenous bacteria in wastewater effluent on microalgal growth, three microalgae, Chlamydomonas reinhardtii, Chlorella vulgaris, and Euglena gracilis, were cultured in two municipal wastewater effluents and one swine wastewater effluent with and without indigenous bacteria for 7 days. All microalgae grew better in all effluents with indigenous bacteria than without bacteria. Biomass production of C. reinhardtii, C. vulgaris, and E. gracilis increased > 1.5, 1.8–2.8, and > 2.1-fold, respectively, compared to the axenic cultures of each microalga. The in situ indigenous bacterial communities in the effluents therefore promoted the growth of the three microalgae during 7-day cultures. Furthermore, the total numbers of bacterial 16S rRNA genes in the 7-day microalgae–effluent cultures were 109‒793 times the initial numbers. These results suggest that the three microalgae produced and supplied organic carbon that supported bacterial growth in the effluent. At the phylum and class levels, Proteobacteria (Alphaproteobacteria and Betaproteobacteria) and Bacteroidetes (Sphingobacteriia and Saprospirae) were selectively enriched in all microalgae–effluent cultures. The enriched core bacterial families and genera were functions of the microalgal species and effluents. These results suggest that certain members of the bacterial community promote the growth of their “host” microalgal species. To enhance their own growth, microalgae may be able to selectively stimulate specific bacterial groups from among the in situ indigenous bacterial community found in wastewater effluent (i.e., microalgae growth-promoting bacteria: MGPB). The MGPB from effluent cultures could be used as “probiotics” to enhance microalgal growth in effluent culture. Wastewater effluent may therefore be a valuable resource, not only of nutrients, but also of MGPB to enable more efficient microalgal biomass production.

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Growth promotion of three microalgae, Chlamydomonas reinhardtii, Chlorella vulgaris and Euglena gracilis, by in situ indigenous bacteria in wastewater effluent.

Paullinia cupana is associated with a diverse community of pathogenic and endophytic microorganisms. We isolated and identified endophytic fungal communities from the roots and seeds of P. cupana genotypes susceptible and tolerant to anthracnose that grow in two sites of the Brazilian Amazonia forest. We assessed the antibacterial, antitumor and genotoxic activity in vitro of compounds isolated from the strains Trichoderma asperellum (1BDA) and Diaporthe phaseolorum (8S). In concert, we identified eight fungal species not previously reported as endophytes; some fungal species capable of inhibiting pathogen growth; and the production of antibiotics and compounds with bacteriostatic activity against Pseudomonas aeruginosa in both susceptible and multiresistant host strains. The plant genotype, geographic location and specially the organ influenced the composition of P. cupana endophytic fungal community. Together, our findings identify important functional roles of endophytic species found within the microbiome of P. cupana. This hypothesis requires experimental validation to propose management of this microbiome with the objective of promoting plant growth and protection.

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Diversity of cultivable fungal endophytes in Paullinia cupana (Mart.) Ducke and bioactivity of their secondary metabolites.

Streptomyces griseocarneus R132 controls phytopathogens and promotes growth of pepper (Capsicum annuum)

Butyrolactone-I (ZB5-1) from the coral-derived fungus Aspergillus terreus was investigated in this study to estimate its anti-neuroinflammatory effects on lipopolysaccharide (LPS)-induced BV-2 microglia cells. MTT assay indicated that ZB5-1 in tested concentrations had no cytotoxicity on BV-2 cells, and significantly reduced the production of nitric oxide (NO), measured using Griess reagent, and interleukin-1 beta (IL-1β), detected by enzyme-linked immunosorbent assay (ELISA). ZB5-1 also down-regulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner by Western blot analysis. Moreover, the effect of ZB5-1 on the nuclear factor-κB (NF-κB) signaling pathway was studied via the expression of phosphorylation of NF-κB p65 and inhibitor of NF-κB (IκB), and the nuclear translocation of NF-κB p65 respectively. The results showed that ZB5-1 could inhibit the phosphorylation of p65 and IκB. Furthermore, molecular docking study suggested that ZB5-1 bound at the active sites of NF-κB to prevent its translocation to the nucleus. Therefore, we suggest ZB5-1 has a potential to reduce the anti-inflammatory response in LPS-induced BV-2 cells.

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Butyrolactone-I from Coral-Derived Fungus Aspergillus terreus Attenuates Neuro-Inflammatory Response via Suppression of NF-κB Pathway in BV-2 Cells.

The compounds terrein (1), butyrolactone I (2), and butyrolactone V (3) were isolated from the ethyl acetate extract (EtOAc) of the endophytic fungus Aspergillus terreus—F7 obtained from Hyptis suaveolens (L.) Poit. The extract and the compounds presented schistosomicidal activity against Schistosoma mansoni; at 100 µg/mL for EtOAc extract, 1297.3 µM for compound 1, 235.6 µM for compound 2, and 454.1 µM for compound 3, they killed 100% of the parasites after 72 h of treatment. Compounds 1, 2, and 3 exerted moderate leishmanicidal activity against Leishmania amazonensis (IC50 ranged from 23.7 to 78.6 µM). At 235.6 and 227.0 µM, compounds 2 and 3, respectively, scavenged 95.92 and 95.12% of the DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), respectively. Regarding the cytotoxicity against the breast tumor cell lines MDA-MB-231 and MCF-7, compound 2 gave IC50 of 34.4 and 17.4 µM, respectively, while compound 3 afforded IC50 of 22.2 and 31.9 µM, respectively. At 117.6 µM, compound 2 inhibited the growth of and killed the pathogen Escherichia coli (ATCC 25922). Compounds 1, 2, and 3 displayed low toxicity against the normal line of human lung fibroblasts (GM07492A cells), with IC50 of 15.3 × 103, 3.4 × 103, and 5.8 × 103 µM, respectively. This is the first report on (i) the in vitro schistosomicidal and leishmanicidal activities of the EtOAc extract of A. terreus—F7 and compounds 1, 2, and 3; and (ii) the antitumor activity of compounds 2 and 3 against MDA-MB-231 and MCF-7 cells.

Samuel Vandresen Filho

Papers

Bioactive compounds of Aspergillus terreus-F7, an endophytic fungus from Hyptis suaveolens (L.) Poit.