Aflatoxin Biosynthetic Pathway and Pathway Genes

Yu, Jiujiang; Ehrlich, Kenneth C.

doi:10.5772/23034

Cited by 20 publications

(27 citation statements)

References 188 publications

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“…Even if the exact mechanism of action has not yet been completely elucidated, a few studies already demonstrated that some of these natural products can inhibit AFB1 production by a transcriptional down-regulation of the genes involved in AFB1 synthesis [11][12][13][14][15][16][17][18]. Aflatoxins are the product of a complex biosynthesis pathway involving at least 27 enzymatic reactions [19][20][21][22][23][24]. The genes coding for these enzymes are grouped in a cluster and their expression is coordinated by two cluster-specific regulators: aflR and aflS [25,26].…”

Section: Introductionmentioning

confidence: 99%

Aflatoxin Biosynthesis and Genetic Regulation: A Review

Caceres

Khoury

et al. 2020

Toxins

215

177

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The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway.

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Section: Introductionmentioning

confidence: 99%

Aflatoxin Biosynthesis and Genetic Regulation: A Review

Caceres

Khoury

et al. 2020

Toxins

215

177

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“…We also found the ability of lovastatin, a polyketide biosynthesis product [19], to block melanin production in a phytopathogenic fungus Pyricularia oryzae [20]. It suggests that statins, like amino acid phosphoanalogues, may be considered as potential inhibitors of the polyketide biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

SOME NATURAL AND SYNTHETIC COMPOUNDS INHIBITING THE BIOSYNTHESIS OF AFLATOXIN B1 AND MELANIN IN Aspergillus flavus

Dzhavakhiya¹,

Voinova²,

Popletaeva³

et al. 2016

S-h. biol.

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A b s t r a c tThe control of the mycotoxin contamination of agricultural products represents a serious problem of the global food and feed industry. Aflatoxin B1 (AFB1) is one of the most dangerous mycotoxins due to its hepatotoxicity, carcinogenicity, and temperature resistance. Thus, the search for substances able to block its biosynthesis and, therefore, to prevent the toxin accumulation in food and feed is still relevant. This paper is devoted to the study of the ability of some natural and synthesized compounds to block the biosynthesis of AFB1 and/or melanin (both are secondary metabolites, which have common intermediates and common initial stages of the polyketide biosynthetic pathway) in toxigenic Aspergillus flavus. The studied compounds included lovastatin, and several commercial compounds: (aminoethyl)thiophosphonic acid, (aminomethyl)thiophosphonic acid, alafosfalin, (1-aminoethyl)phosphonic acid, and N-hydroxyputrescine. A mutant Aspergillus terreus strain 45-50 obtained earlier from the A. terreus ATCC 20542 was used as the lovastatin producer. N-hydroxyputrescine and some phosphoanalogues of amino acids were assessed by their influence on the pigmentation of fungal colonies grown on solid medium and on the specific AFB1 content in cultural broth determined after the cultivation of a fungus on liquid nutrition medium. According to the obtained results, the studied compounds were divided into three groups. To reveal changes in the colony morphology, toxigenic A. flavus strain AF11 was cultivated on agarized medium. Concentrations of tested compounds in the medium varied from 0.0001 to 0.1 % depending on their activity. To determine the effect of tested compounds on the AFB1 production, AF11 was cultivated for 170 h in a liquid Payne-Hagler medium. Solutions of the tested compounds were added to the medium up to the final concentration of 0.001-0.1 % (commercial compounds) or 0.0001 to 0.001 % (lovastatin). The efficiency of the AFB1 biosynthesis stimulation/inhibition was assessed by the comparison of its content in the cultural broth in the experimental and control (medium without additions) variants. In addition, the effect of lovastatin on the AFB1 accumulation in wheat grain contaminated with A. flavus AF11 was assessed. The performed screening allowed us to divide the studied compounds into three groups. The supplement of the nutrition medium with (aminoethyl)thiophosphonic acid, (aminomethyl)thiophosphonic acid, and alafosfalin caused a significant decrease in the AFB1 production, but did not influenced on the colony pigmentation. N-hydroxyputrescine and (1-aminoethyl)phosphonic acid were able to partially or completely block the melanin biosynthesis with the simultaneous increase in the AFB1 production. Lovastatin completely blocked both AFB1 and melanin production even at low concentrations (0.0005 %). Therefore, compounds from the first and second groups inhibit the AFB1 or melanin biosynthesis, respectively, via the blocking of stages located after the point of divergence of the correspon...

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“…The biosynthesis of aflatoxin from primary metabolites requires activity at least 23 conserved genes bunched together in a single gene cluster . The sequence of a controlling element, aflR , in the cluster can vary, possibly resulting in different levels of synthesis .…”

Section: Aspergillus Infection and Aflatoxin Biosynthesismentioning

confidence: 99%

“…The biosynthesis of aflatoxin from primary metabolites requires activity at least 23 conserved genes bunched together in a single gene cluster. 7,8 The sequence of a controlling element, aflR, in the cluster can vary, possibly resulting in different levels of synthesis. 6 When an inverted repeat of aflR was transgenically inserted into Aspergillus, the biosynthesis of versicolorin A, a key intermediary in aflatoxin production, was (qualitatively) suppressed.…”

Section: Aspergillus Infection and Aflatoxin Biosynthesismentioning

confidence: 99%

Suppressing aflatoxin biosynthesis is not a breakthrough if not useful

Gressel

Polturak

2017

Pest Management Science

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Liver-affecting, carcinogenic aflatoxins produced by Aspergillus spp. are a major problem, especially in the humid developing world where storage conditions are often optimal for the fungi. Peanuts and maize have been transformed with RNAi constructs targeting Aspergillus flavus polyketide-synthase, an early key enzyme in aflatoxin biosynthesis. Aflatoxin biosynthesis was suppressed in developing immature grain, less so in late maturing grain, and it is doubtful that the technology will be effective in near dry mature grain. The infected grain was still mouldy. As Aspergillus that infects grain preharvest can continue to grow and produce aflatoxin in poorly stored grain, and grain storage insects vector further infections, this technology seems to have little potential utility in the humid tropics. The biotechnological approaches of RNAi directly targeting Aspergillus, coupled with transgenic insecticidal proteins should be far more effective. These biotechnological approaches can be used in tandem with the RNAi against polyketide-synthase, as well as with irradiation, biocontrol and better grain drying and hermetic dry storage in a controlled atmosphere.

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Aflatoxin Biosynthetic Pathway and Pathway Genes

Cited by 20 publications

References 188 publications

Aflatoxin Biosynthesis and Genetic Regulation: A Review

Aflatoxin Biosynthesis and Genetic Regulation: A Review

SOME NATURAL AND SYNTHETIC COMPOUNDS INHIBITING THE BIOSYNTHESIS OF AFLATOXIN B1 AND MELANIN IN Aspergillus flavus

Suppressing aflatoxin biosynthesis is not a breakthrough if not useful

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