Medium-Chain Fatty Acids Affect Citrinin Production in the Filamentous Fungus Monascus ruber
| Autor: | Estelle Barbier, Jean Marie François, Hassan Hajjaj, Alain Klaebe, Gérard Goma, Philippe Blanc |
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| Rok vydání: | 2000 |
| Předmět: |
Indoles
Stereochemistry Glutamic Acid Acetates Applied Microbiology and Biotechnology Glutarates chemistry.chemical_compound Polyketide Ascomycota Polyketide synthase Peroxisomes Aspergillus terreus Penicillium citrinum chemistry.chemical_classification Hexanoic acid Carbon Isotopes Ecology biology Fatty Acids Fatty acid Pigments Biological Ketones Physiology and Biotechnology biology.organism_classification Citrinin Amino acid Glucose chemistry Biochemistry biology.protein Caprylates Food Science Biotechnology |
| Zdroj: | Applied and Environmental Microbiology. 66:1120-1125 |
| ISSN: | 1098-5336 0099-2240 |
| Popis: | In filamentous fungi, many secondary metabolites with complex chemical structures are synthesized from the polyketide pathway (26, 29). These metabolites display a wide range of biological activities, including antibiotic, antifungal, immunosuppressive, and anticancer properties. In this respect, Monascus ruber is an interesting filamentous fungus which can excrete a broad spectrum of colored pigments that are routinely used in Asia as food additives. From previous works (12, 29), a scheme of the hypothetical routes for the biosynthesis of these various pigments in filamentous fungi is depicted in Fig. Fig.1.1. The condensation of 1 mol of acetate with 5 mol of malonate leads to the formation of a hexaketide chromophore by the polyketide synthase. Then a medium-chain fatty acid such as octanoic acid, likely produced by the fatty acid biosynthetic pathway, is bound to the chromophore structure by a trans-esterification reaction to generate the orange pigment monascorubrin (or rubropunctatin upon trans-esterification with hexanoic acid). The reduction of the orange pigment gives rise to the yellow pigment ankaflavin from monascorubrin (or monascin from rubropunctatin), whereas red pigments (monascorubramine and rubropunctamine) are produced by amination of orange pigments with NH3 units (18). All these pigments remain essentially intracellular because of their high hydrophobicity. They are eventually excreted in the medium after reacting with an NH2 unit of amino acids (13, 32). For this reason, glutamate has been the most useful amino acid, since it can serve both as a carbon and as a nitrogen source (21, 22). FIG. 1 Scheme of the hypothetic metabolic routes leading to the final structure of the water-soluble red pigment N-glutarylmonascorubramine in M. ruber. While these pigments are traditionally produced by solid-state fermentation on rice or bread crumbs, studies involving submerged fermentation have recently revealed that, together with pigment production, M. ruber excretes a mycotoxin, namely, citrinin (6), which has antibiotic properties against gram-positive bacteria. However, the nephrotoxic and hepatotoxic properties of this toxin (2, 4) compromise the use of red pigments as natural colorants for food technology. Therefore, biochemical and genetic studies should be undertaken to prevent the formation of citrinin while enhancing that of pigments. As a first step along this line, we recently demonstrated that the biosynthesis of citrinin originates from a tetraketide instead of a pentaketide as was found in Aspergillus terreus and Penicillium citrinum (14). Since pigments are produced from a hexaketide, this suggested the existence of a branch point at the tetraketide level which could account for a differential production of pigments and citrinin during the growth of M. ruber. However, the enzymes catalyzing the reactions at this junction have not been characterized yet. Another method to potentially enhance pigment synthesis and eventually reduce that of citrinin came from the suggestion given above that the synthesis of pigments may arise from a combination of the polyketide and fatty acid synthase pathways (see Fig. Fig.1).1). Therefore, it might be feasible to short-circuit the need for endogenous synthesis of these medium-chain fatty acids by adding them to the growth medium. We addressed this question by determining the fates of [1-13C]-, [2-13C]-, or [1,2-13C]acetate and [1-13C]octanoate during the biosynthesis of pigments using 13C nuclear magnetic resonance (NMR), and we investigated the effects of medium- and long-chain fatty acids on pigment and citrinin production. Our results showed that, contrary to expectations, the synthesis of pigments was barely affected whereas the production of citrinin was strongly inhibited, likely by a hydrogen peroxide-mediated degradation of the toxin due to fatty acid-induced peroxisome proliferation. |
| Databáze: | OpenAIRE |
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