Cytotoxic and Antibiotic Cyclic Pentapeptide from an Endophytic <i>Aspergillus tamarii</i> of <i>Ficus carica</i>

Aspergillus is one of the economically most important fungal genera. Recently, the ICN adopted the single name nomenclature which has forced mycologists to choose one name for fungi (e.g. Aspergillus, Fusarium, Penicillium, etc.). Previously two proposals for the single name nomenclature in Aspergillus were presented: one attributes the name “Aspergillus” to clades comprising seven different teleomorphic names, by supporting the monophyly of this genus; the other proposes that Aspergillus is a non-monophyletic genus, by preserving the Aspergillus name only to species belonging to subgenus Circumdati and maintaining the sexual names in the other clades. The aim of our study was to test the monophyly of Aspergilli by two independent phylogenetic analyses using a multilocus phylogenetic approach. One test was run on the publicly available coding regions of six genes (RPB1, RPB2, Tsr1, Cct8, BenA, CaM), using 96 species of Penicillium, Aspergillus and related taxa. Bayesian (MrBayes) and Ultrafast Maximum Likelihood (IQ-Tree) and Rapid Maximum Likelihood (RaxML) analyses gave the same conclusion highly supporting the monophyly of Aspergillus. The other analyses were also performed by using publicly available data of the coding sequences of nine loci (18S rRNA, 5,8S rRNA, 28S rRNA (D1-D2), RPB1, RPB2, CaM, BenA, Tsr1, Cct8) of 204 different species. Both Bayesian (MrBayes) and Maximum Likelihood (RAxML) trees obtained by this second round of independent analyses strongly supported the monophyly of the genus Aspergillus. The stability test also confirmed the robustness of the results obtained. In conclusion, statistical analyses have rejected the hypothesis that the Aspergilli are non-monophyletic, and provided robust arguments that the genus is monophyletic and clearly separated from the monophyletic genus Penicillium. There is no phylogenetic evidence to split Aspergillus into several genera and the name Aspergillus can be used for all the species belonging to Aspergillus i.e. the clade comprising the subgenera Aspergillus, Circumdati, Fumigati, Nidulantes, section Cremei and certain species which were formerly part of the genera Phialosimplex and Polypaecilum. Section Cremei and the clade containing Polypaecilum and Phialosimplex are proposed as new subgenera of Aspergillus. The phylogenetic analysis also clearly shows that Aspergillus clavatoflavus and A. zonatus do not belong to the genus Aspergillus. Aspergillus clavatoflavus is therefore transferred to a new genus Aspergillago as Aspergillago clavatoflavus and A. zonatus was transferred to Penicilliopsis as P. zonata. The subgenera of Aspergillus share similar extrolite profiles indicating that the genus is one large genus from a chemotaxonomical point of view. Morphological and ecophysiological characteristics of the species also strongly indicate that Aspergillus is a polythetic class in phenotypic characters.

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“…1Even though Ma et al . (2016) identified their strain as Aspergillus tamarii , their strain was clearly an A. fumigatus .…”

Section: Figmentioning

confidence: 99%

Aspergillus is monophyletic: Evidence from multiple gene phylogenies and extrolites profiles

Kocsubé¹,

Perrone²,

Magistà³

et al. 2016

Studies in Mycology

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“…Plant-associated microorganisms are known to produce a variety of metabolites with novel structures and interesting biological activities (4)(5)(6)(7)(8). MA1 isolated from the fungus A. niger has been found to possess a range of bioactive properties, which includes enhancing fibrinolytic activity, and acting as an antibacterial/viral/fungal agent (13)(14)(15)(16)(17)(18). Furthermore, MA1 exhibits a strong cytotoxic effect against various human cancer cell lines (9,(22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the inhibitor of the phosphatidylinositol 3-kinase signaling pathway abolished the enhancement of cellular fibrinolytic activity by MA1 in human leukemia U937 cells. That said, the inhibitor of MAPK signaling showed minimal effects on MA1 treated leukemia cells (13). MAPK signaling pathways, including ERK1/2, JNK, and p38 MAPK, play a critical role in many physiologic processes, including cell growth, differentiation, migration, proliferation, apoptosis, and cell cycle progression (29,30).…”

Section: Discussionmentioning

confidence: 99%

“…Malformin A1 (MA1) is a bicyclic pentapeptide containing five amino acids: L-isoleucine, L-valine, D-leucine, and two D-cysteines (12). MA1 is the most well-studied out of the malformin subtypes, and its various biological activities have been reported previously, including causing malformations in plants, having some antibacterial effects (13)(14)(15), enhancing cellular fibrinolytic activity (16 -18), preventing IL-1-induced procoagulant reaction (19,20), and inhibiting the cell cycle at G2 checkpoint followed by DNA damage (21,22). Additionally, the anticancer activity of MA1 has been reported in various human cancer cells including colorectal cancer (9,22-24).…”

Section: Introductionmentioning

confidence: 99%

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Malformin A1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through stimulation of the p38 signaling pathway

Park

et al. 2017

International Journal of Oncology

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Malformin A1 (MA1), a cyclic pentapeptide isolated from Aspergillus niger, has been found to possess a range of bioactive properties including antibacterial activity. However, it is unclear whether MA1 exerts an anticancer effect or not. In this study, we conducted in vitro experiments to investigate its anticancer properties in human colorectal cancer cells. The effect of MA1 on human colorectal cancer cells, SW480 and DKO1, was examined by the WST-1 cell viability assay, inverted microscopy, 5-bromo-2-deoxyuridine (BrdU) incorporation, flow cytometry, DNA fragmentation, wound healing, Transwell assays, and western blotting. MA1 treatment showed potent cytotoxic activities on human colorectal cancer cells. MA1 treatment induced apoptosis by activating the poly(ADP-ribose) polymerase (PARP), caspase‑3, -7, and -9. MA1 treatment led to the increase in p53 upregulated modulator of apoptosis (PUMA) and the decrease in X-linked inhibitor of apoptosis protein (XIAP) and Survivin. In addition, MA1 treatment induced cell cycle arrest in the sub-G1 phase. The pan-caspase inhibitor, Z‑VAD‑FMK, attenuated these MA1-induced apoptotic effects on human colorectal cancer cells. Moreover, MA1 treatment suppressed tumor cell migration and invasion. The phosphorylation level of p38 was upregulated by MA1 treatment, and the inhibitor of p38, SB203580, attenuated the MA1-induced p38 phosphorylation as well as caspase‑3 and PARP activation. These results indicate that MA1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through the stimulation of the p38 signaling pathway.

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“…This promotion of growth by endophytic action may be a consequence of nitrogen fixation, synthesis of phytohormones, biocontrol of phytopathogens through the synthesis of antibiotics or siderophores, competition for nutrients, and the induction of systemic disease resistance (Ahmad et al, 2016). However, the bioprospection and characterization of these microorganisms, associated with the most diverse plant species, is aimed not only at obtaining strains of agronomic importance but also at the identification of species that produce metabolites with potential for the synthesis of antibiotics (e.g., Ma et al, 2016), as well as potential for obtaining biotechnologically important chemicals.…”

Section: Agricultural Technological Microbiologymentioning

confidence: 99%

Technological Microbiology: Development and Applications

Vitorino

Bessa

2017

Front. Microbiol.

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Over thousands of years, modernization could be predicted for the use of microorganisms in the production of foods and beverages. However, the current accelerated pace of new food production is due to the rapid incorporation of biotechnological techniques that allow the rapid identification of new molecules and microorganisms or even the genetic improvement of known species. At no other time in history have microorganisms been so present in areas such as agriculture and medicine, except as recognized villains. Currently, however, beneficial microorganisms such as plant growth promoters and phytopathogen controllers are required by various agricultural crops, and many species are being used as biofactories of important pharmacological molecules. The use of biofactories does not end there: microorganisms have been explored for the synthesis of diverse chemicals, fuel molecules, and industrial polymers, and strains environmentally important due to their biodecomposing or biosorption capacity have gained interest in research laboratories and in industrial activities. We call this new microbiology Technological Microbiology, and we believe that complex techniques, such as heterologous expression and metabolic engineering, can be increasingly incorporated into this applied science, allowing the generation of new and improved products and services.

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Cytotoxic and Antibiotic Cyclic Pentapeptide from an Endophytic Aspergillus tamarii of Ficus carica

Cited by 67 publications

References 17 publications

Aspergillus is monophyletic: Evidence from multiple gene phylogenies and extrolites profiles

Aspergillus is monophyletic: Evidence from multiple gene phylogenies and extrolites profiles

Malformin A1 treatment alters invasive and oncogenic phenotypes of human colorectal cancer cells through stimulation of the p38 signaling pathway

Technological Microbiology: Development and Applications

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