Docking analysis of hexanoic acid and quercetin with seven domains of polyketide synthase A provided insight into quercetin-mediated aflatoxin biosynthesis inhibition in Aspergillus flavus

Abstract Aspergillus flavus is known for producing the potent carcinogenic agent aflatoxin. Food contamination with aflatoxins is an important safety concern for agricultural yields. To identify and develop anti-aflatoxigenic agents, studies on phytochemicals as anti-aflatoxigenic agents have been documented including gallic acid. Thus, interaction studies using in-silico tools have been explored to understand the molecular mechanism behind inhibition of aflatoxin biosynthesis by studying the chemical interactions of gallic acid with polyketide synthase A (PksA) of A. flavus. The 3D structure of PksA consisting of seven domains was modeled using a Swiss-Model server followed by docking using Autodock tools-1.5.6 with substrate hexanoic acid and with that to gallic acid. The binding energy (electrostatic, inter-molecular or total internal energy) for gallic acid was lower (-6.09 to -4.79 kcal/mol) in comparison to hexanoic acid (-5.05 to -3.36 kcal/mol). During an interaction with the acyl transferase domain of PksA, both ligands showed H-bond formation at Glu36, Arg8, Thr11 positions. Ligplot analysis showed the formation of 7-H bonds in gallic acid and 3-H bonds in hexanoic acid. In addition, gallic acid showed stable binding with the active site of PksA indicated by steady root mean square deviation through molecular dynamic simulations. The chemistry between gallic acid and polyketide synthase A(PksA) exhibited that Gallic Acid possesses the highest level of binding potential (more number of hydrogen bonds) with PksA domain in comparison to hexanoic acid, a precursor for aflatoxin biosynthesis. Thus, we suggest enzymes from the aflatoxin biosynthetic pathway in aflatoxin-producing Aspergilli could be an important target for potential inhibitors.

Download Full-text

Dual culture of atoxigenic and toxigenic strains of Aspergillus flavus to gain insight into repression of aflatoxin biosynthesis and fungal interaction

Mycotoxin Research ◽

10.1007/s12550-019-00364-w ◽

2019 ◽

Vol 35 (4) ◽

pp. 381-389

Author(s):

Sui Sheng T. Hua ◽

Dan E. Parfitt ◽

Siov Bouy L. Sarreal ◽

Gaganjot Sidhu

Keyword(s):

Aspergillus Flavus ◽

Dual Culture ◽

Aflatoxin Biosynthesis ◽

Toxigenic Strains ◽

Insight Into

Download Full-text

Increased sensitivity of Aspergillus flavus and Aspergillus parasiticus aflatoxin biosynthesis polyketide synthase mutants to UVB light

World Mycotoxin Journal ◽

10.3920/wmj2010.1218 ◽

2010 ◽

Vol 3 (3) ◽

pp. 263-270 ◽

Cited By ~ 3

Author(s):

K. Ehrlich ◽

Q. Wei ◽

D. Bhatnagar

Keyword(s):

Aspergillus Flavus ◽

Polyketide Synthase ◽

Aspergillus Parasiticus ◽

Aflatoxin Contamination ◽

Aflatoxin Biosynthesis ◽

Increased Sensitivity ◽

Isogenic Mutants

One strategy to reduce aflatoxin contamination of maize and cottonseed is to introduce spores of non-aflatoxigenic strains as competitors. Using isogenic mutants we show that, upon 5 or 20 min exposure to 302 nm (UVB) light, the viability of conidia of Aspergillus flavus and Aspergillus parasiticus mutants lacking the ability to accumulate any aflatoxin precursor metabolite is reduced five-fold compared to that of aflatoxin-producing strains or pigmented mutants that accumulate aflatoxin precursors. This result suggests that the long-term viability of introduced non-aflatoxigenic competitor strains may be lower than that of natural aflatoxin-producing isolates when exposed to sunlight.

Download Full-text

Revisiting an Aspergillus flavus Strain Isolated from an Egyptian Sugarcane Field in 1930

Microorganisms ◽

10.3390/microorganisms8111633 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1633

Author(s):

Mohamed F. Abdallah ◽

Kris Audenaert ◽

Sarah De Saeger ◽

Jos Houbraken

Keyword(s):

Aspergillus Flavus ◽

Short Communication ◽

Aflatoxin Contamination ◽

Type B ◽

Prevention Strategies ◽

Sugarcane Field ◽

Host Pathogen Interaction ◽

Sugarcane Crop ◽

Insight Into ◽

Shed Light

The aflatoxin type B and G producer Aspergillus novoparasiticus was described in 2012 and was firstly reported from sputum, hospital air (Brazil), and soil (Colombia). Later, several survey studies reported the occurrence of this species in different foods and other agricultural commodities from several countries worldwide. This short communication reports on an old fungal strain (CBS 108.30), isolated from Pseudococcus sacchari (grey sugarcane mealybug) from an Egyptian sugarcane field in (or before) 1930. This strain was initially identified as Aspergillus flavus; however, using the latest taxonomy schemes, the strain is, in fact, A. novoparasiticus. These data and previous reports indicate that A. novoparasiticus is strongly associated with sugarcane, and pre-harvest biocontrol approaches with non-toxigenic A. novoparasiticus strains are likely to be more successful than those using non-toxigenic A. flavus strains. Further studies on the association between A. novoparasiticus and Pseudococcus sacchari might shed light on the distribution (and aflatoxin contamination) of this species in sugarcane. Additionally, the interaction between A. novoparasiticus, Pseudococcus sacchari, and sugarcane crop under different scenarios of climate change will be critical in order to get more insight into the host–pathogen interaction and host resistance and propose appropriate prevention strategies to decrease mycotoxin contamination and crop loss due to A. novoparasiticus attack.

Download Full-text

Carbon catabolite repression gene creA regulates morphology, aflatoxin biosynthesis and virulence in Aspergillus flavus

Fungal Genetics and Biology ◽

10.1016/j.fgb.2018.04.008 ◽

2018 ◽

Vol 115 ◽

pp. 41-51 ◽

Cited By ~ 19

Author(s):

Opemipo Esther Fasoyin ◽

Bin Wang ◽

Mengguang Qiu ◽

Xiaoyun Han ◽

Kuang-Ren Chung ◽

...

Keyword(s):

Aspergillus Flavus ◽

Catabolite Repression ◽

Carbon Catabolite Repression ◽

Aflatoxin Biosynthesis

Download Full-text

Vibrio gazogenes inhibits aflatoxin production through downregulation of aflatoxin biosynthetic genes in Aspergillus flavus

PhytoFrontiers™ ◽

10.1094/phytofr-09-21-0067-r ◽

2022 ◽

Author(s):

Shyam L. Kandel ◽

Rubaiya Jesmin ◽

Brian M. Mack ◽

Rajtilak Majumdar ◽

Matthew K. Gilbert ◽

...

Keyword(s):

Secondary Metabolites ◽

Secondary Metabolite ◽

Aspergillus Flavus ◽

Fungal Biomass ◽

Expression Profiles ◽

Health Hazard ◽

Gene Clusters ◽

Aflatoxin Contamination ◽

Aflatoxin Biosynthesis ◽

Control Samples

Aspergillus flavus is an opportunistic pathogen of oilseed crops such as maize, peanut, cottonseed, and tree nuts and produces carcinogenic secondary metabolites known as aflatoxins during seed colonization. Aflatoxin contamination not only reduces the value of the produce but also is a health hazard to humans and animals. Previously, we observed inhibition of A. flavus aflatoxin biosynthesis upon exposure to the marine bacterium, Vibrio gazogenes (Vg). In this study, we used RNA sequencing to examine the transcriptional profiles of A. flavus treated with both live and heat-inactivated dead Vg and control samples. Fungal biomass, total accumulated aflatoxins, and expression profiles of genes constituting secondary metabolite biosynthetic gene clusters were determined at 24, 30, and 40 h after treatment. Statistically significant reductions in total aflatoxins were detected in Vg-treated samples as compared to control samples at 40 h. But no statistical difference in fungal biomass was observed upon these treatments. The Vg treatments were most effective on aflatoxin biosynthesis as was reflected in significant downregulation of majority of the genes in the aflatoxin gene cluster including the aflatoxin pathway regulator gene, aflR. Along with aflatoxin genes, we also observed significant downregulation in some other secondary metabolite gene clusters including cyclopiazonic acid and aflavarin, suggesting that the treatment may inhibit other secondary metabolites as well. Finally, a weighted gene correlation network analysis identified an upregulation of ten genes that were most strongly associated with Vg-dependent aflatoxin inhibition and provide a novel start-point in understanding the mechanisms that result in this phenomenon.

Download Full-text

Inhibition of Aflatoxin Biosynthesis by Organophosphorus Compounds

Journal of Food Protection ◽

10.4315/0362-028x-43.5.381 ◽

1980 ◽

Vol 43 (5) ◽

pp. 381-384 ◽

Cited By ~ 23

Author(s):

M. F. DUTTON ◽

M. S. ANDERSON

Keyword(s):

Aspergillus Flavus ◽

Organophosphorus Compound ◽

Organophosphorus Compounds ◽

Culture Fluid ◽

Aflatoxin Production ◽

The Other ◽

Aflatoxin Biosynthesis ◽

Inhibition Effect ◽

Type Activity ◽

Acetate Derivative

The effect of a range of organophosphorus and various other compounds on production of aflatoxin by Aspergillus flavus was investigated. Five organophosphorus compounds - Chlormephos, Ciodrin, Naled, Phosdrin and Trichlorphon- at concentrations of 20 and 100 μg/ml of culture fluid were found to have activity similar to Dichlorvos, in that they lowered the level of aflatoxin produced and caused formation of several anthraquinone pigments. Two of these pigments have not previously been described, one was named Versicol and a suggested structure is presented, whilst the other compound was shown to be its acetate derivative. A rationale is suggested for the required elements of structure, which are necessary for an organophosphorus compound to have Dichlorvos-type activity. Two unrelated compounds, ammonium nitrate and Tridecanone were also found to elicit Dichlorvos-type activity. It is likely that tridecanone or its breakdown products competitively inhibit enzymes involved in aflatoxin biosynthesis. It is possible that this inhibition effect explains the lowering of aflatoxin production in lipid-rich commodities infected by A. flavus.

Download Full-text

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus

Environmental Microbiology ◽

10.1111/1462-2920.14825 ◽

2019 ◽

Vol 21 (12) ◽

pp. 4792-4807 ◽

Cited By ~ 3

Author(s):

Guang Yang ◽

Yuewei Yue ◽

Silin Ren ◽

Mingkun Yang ◽

Yi Zhang ◽

...

Keyword(s):

Aspergillus Flavus ◽

Lysine Acetylation ◽

Aflatoxin Biosynthesis

Download Full-text

Pyridoxal-5′-phosphate–dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914777117 ◽

2019 ◽

Vol 117 (2) ◽

pp. 1174-1180 ◽

Cited By ~ 3

Author(s):

Guang Zhi Dai ◽

Wen Bo Han ◽

Ya Ning Mei ◽

Kuang Xu ◽

Rui Hua Jiao ◽

...

Keyword(s):

Polyketide Synthase ◽

Complex Structure ◽

Genome Mining ◽

Biosynthetic Gene Cluster ◽

Major Facilitator Superfamily ◽

Molecular Architecture ◽

Widespread Occurrence ◽

Indolizidine Alkaloids ◽

Major Facilitator ◽

Insight Into

Indolizidine alkaloids such as anticancer drugs vinblastine and vincristine are exceptionally attractive due to their widespread occurrence, prominent bioactivity, complex structure, and sophisticated involvement in the chemical defense for the producing organisms. However, the versatility of the indolizidine alkaloid biosynthesis remains incompletely addressed since the knowledge about such biosynthetic machineries is only limited to several representatives. Herein, we describe the biosynthetic gene cluster (BGC) for the biosynthesis of curvulamine, a skeletally unprecedented antibacterial indolizidine alkaloid from Curvularia sp. IFB-Z10. The molecular architecture of curvulamine results from the functional collaboration of a highly reducing polyketide synthase (CuaA), a pyridoxal-5′-phosphate (PLP)-dependent aminotransferase (CuaB), an NADPH-dependent dehydrogenase (CuaC), and a FAD-dependent monooxygenase (CuaD), with its transportation and abundance regulated by a major facilitator superfamily permease (CuaE) and a Zn(II)Cys6 transcription factor (CuaF), respectively. In contrast to expectations, CuaB is bifunctional and capable of catalyzing the Claisen condensation to form a new C–C bond and the α-hydroxylation of the alanine moiety in exposure to dioxygen. Inspired and guided by the distinct function of CuaB, our genome mining effort discovers bipolamines A−I (bipolamine G is more antibacterial than curvulamine), which represent a collection of previously undescribed polyketide alkaloids from a silent BGC in Bipolaris maydis ATCC48331. The work provides insight into nature’s arsenal for the indolizidine-coined skeletal formation and adds evidence in support of the functional versatility of PLP-dependent enzymes in fungi.

Download Full-text

Morphological and Transcriptomic Analysis of the Inhibitory Effects of Lactobacillus plantarum on Aspergillus flavus Growth and Aflatoxin Production

Toxins ◽

10.3390/toxins11110636 ◽

2019 ◽

Vol 11 (11) ◽

pp. 636 ◽

Cited By ~ 3

Author(s):

Zhao ◽

Zhang ◽

Folly ◽

Chang ◽

Wang ◽

...

Keyword(s):

Lactobacillus Plantarum ◽

Aspergillus Flavus ◽

Aflatoxin Production ◽

Inhibitory Effect ◽

Transcriptional Level ◽

Sequencing Data ◽

Inhibitory Effects ◽

Cell Wall Polysaccharides ◽

Colony Forming Units ◽

Insight Into

Lactobacillus plantarum, as a natural bio-preservative, has attracted a great deal of attention in recent years. In this study, 22 L. plantarum strains were tested against the aflatoxin-producing fungus, Aspergillus flavus; strain IAMU80070 showed the highest antifungal activity. At a concentration of 5 × 105 colony-forming units (CFU) mL−1, it completely inhibited A. flavus growth and decreased aflatoxin production by 93%. Furthermore, ultrastructural examination showed that IAMU80070 destroyed the cellular structure of hyphae and spores. To explore the inhibitory effect of IAMU80070 on A. flavus at the transcriptional level, transcriptome data were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The aflatoxin biosynthetic process was the most significantly downregulated functional category, while genes implicated in the synthesis and organization of cell wall polysaccharides were upregulated. Quantitative real-time PCR results verified the credibility and reliability of the RNA sequencing data. These results provided insight into the transcriptome of A. flavus in response to the antagonistic effects of L. plantarum IAMU80070.

Download Full-text