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      Predicted Roles of the Uncharacterized Clustered Genes in Aflatoxin Biosynthesis

      review-article
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      Publication date (Electronic):
      Journal: Toxins
      Publisher: Molecular Diversity Preservation International
      Keywords: biosynthesis, oxidation, enzymes, Aspergillus, secondary metabolism

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          Abstract

          Biosynthesis of the toxic and carcinogenic aflatoxins (AFs) requires the activity of more than 27 enzymes. The roles in biosynthesis of newly described enzymes are discussed in this review. We suggest that HypC catalyzes the oxidation of norsolorinic acid anthrone; AvfA (AflI), the ring-closure step in formation of hydroxyversicolorone; HypB, the second oxidation step in conversion of O-methylsterigmatocystin to AF; and HypE and NorA (AflE), the final two steps in AFB 1 formation. HypD, an integral membrane protein, affects fungal development and lowers AF production while AflJ (AflS), has a partial methyltransferase domain that may be important in its function as a transcriptional co-activator.

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          Fungal secondary metabolism - from biochemistry to genomics.

          Nancy Keller, Geoffrey Turner, Joan W. Bennett (2005)
          Much of natural product chemistry concerns a group of compounds known as secondary metabolites. These low-molecular-weight metabolites often have potent physiological activities. Digitalis, morphine and quinine are plant secondary metabolites, whereas penicillin, cephalosporin, ergotrate and the statins are equally well known fungal secondary metabolites. Although chemically diverse, all secondary metabolites are produced by a few common biosynthetic pathways, often in conjunction with morphological development. Recent advances in molecular biology, bioinformatics and comparative genomics have revealed that the genes encoding specific fungal secondary metabolites are clustered and often located near telomeres. In this review, we address some important questions, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
          Article 0 comments Cited 474 times – based on 0 reviews     Review now
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            VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism.

            Özgür Bayram, Sven Krappmann, Min Ni … (2008)
            Differentiation and secondary metabolism are correlated processes in fungi that respond to light. In Aspergillus nidulans, light inhibits sexual reproduction as well as secondary metabolism. We identified the heterotrimeric velvet complex VelB/VeA/LaeA connecting light-responding developmental regulation and control of secondary metabolism. VeA, which is primarily expressed in the dark, physically interacts with VelB, which is expressed during sexual development. VeA bridges VelB to the nuclear master regulator of secondary metabolism, LaeA. Deletion of either velB or veA results in defects in both sexual fruiting-body formation and the production of secondary metabolites.
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              Aspergillus flavus: human pathogen, allergen and mycotoxin producer.

              M T Hedayati, A Pasqualotto, P Warn … (2007)
              Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the genus. In certain locales and hospitals, Aspergillus flavus is more common in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is the second leading cause of invasive aspergillosis and it is the most common cause of superficial infection. Experimental invasive infections in mice show A. flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum required. Particularly common clinical syndromes associated with A. flavus include chronic granulomatous sinusitis, keratitis, cutaneous aspergillosis, wound infections and osteomyelitis following trauma and inoculation. Outbreaks associated with A. flavus appear to be associated with single or closely related strains, in contrast to those associated with A. fumigatus. In addition, A. flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural compounds ever characterized. Accurate species identification within Aspergillus flavus complex remains difficult due to overlapping morphological and biochemical characteristics, and much taxonomic and population genetics work is necessary to better understand the species and related species. The flavus complex currently includes 23 species or varieties, including two sexual species, Petromyces alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae is completed and available; that of A. flavus in the final stages of annotation. Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of the genomics, taxonomy, population genetics, pathogenicity, allergenicity and antifungal susceptibility of A. flavus are all required.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Toxins (Basel)
                Journal ID (publisher-id): toxins
                Title: Toxins
                Publisher: Molecular Diversity Preservation International
                ISSN (Electronic): 2072-6651
                Publication date Collection: September 2009
                Publication date (Electronic): 25 September 2009
                Volume: 1
                Issue: 1
                Pages: 37-58
                Affiliations
                Southern Regional Research Center, ARS, USDA/1100 Robert E. Lee Blvd, New Orleans, LA 70124, USA; Email: ken.ehrlich@ 123456ars.usda.gov ; Tel.: +1-504-286-4369; Fax: +1-504-286-4419
                Article
                Publisher ID: toxins-01-00037
                DOI: 10.3390/toxins1010037
                PMC ID: 3202775
                PubMed ID: 22069531
                SO-VID: 20e9343f-4d06-4a33-bfd2-67aa819be1f0
                Copyright © © 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 11 August 2009
                Date revision received : 22 September 2009
                Date accepted : 24 September 2009
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: biosynthesis,oxidation,enzymes,aspergillus,secondary metabolism
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: biosynthesis, oxidation, enzymes, aspergillus, secondary metabolism

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