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Eukaryotic Cell doi:10.1128/EC.00362-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The phosphopantetheinyl transferase CfwA/NpgA is required for Aspergillus nidulans secondary metabolism and asexual development

Instituto de Ciencias Básicas, Universidad Veracruzana, Av. Dos Vistas s/n, Carretera Xalapa-Las Trancas, 91000 Veracruz, Xalapa, México; Laboratorio de Alta Tecnología (LATEX), Médicos No. 5, Unidad del Bosque, Xalapa, Ver., México; Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, 04510 México D.F., México, Tel: (5255) 5622 5651, Fax: (5255) 5622 5630, Departamento de Biotecnología, Universidad Autónoma Metropolitana, Av. Michoacán y La Purísima, 09340 México D. F., México; Martin-Luther-University-Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Phytopathology and Plant Protection, Ludwig-Wucherer-Str. 2, D-06099 Halle (Saale), Germany

^* To whom correspondence should be addressed. Email: jaguirre{at}ifc.unam.mx.

	Abstract

Polyketide synthases (PKSs) and/or non-ribosomal peptide synthetases (NRPSs) are central components of secondary metabolism in bacteria, plants and fungi. In filamentous fungi, diverse PKSs and NRPSs participate in the biosynthesis of secondary metabolites such as pigments, antibiotics, siderophores and mycotoxins. However, many secondary metabolites as well as the enzymes involved in their production are yet to be discovered. Both, PKSs and NRPSs require activation by enzyme members of the 4'-phosphopantetheinyl transferase (PPTase) family. Here we report the isolation and characterization of Aspergillus nidulans strains carrying conditional (cfwA2) and null (cfwA) mutant alleles of the cfwA gene, encoding an essential PPTase. We identify the polyketides shamixanthone, emericellin and dehydroaustinol, as well as the sterols ergosterol, peroxiergosterol and cerevisterol in extracts from A. nidulans large-scale cultures. The PPTase CfwA/NpgA was required for production of these polyketide compounds, but dispensable for ergosterol, cerevisterol and for fatty acid biosynthesis. The asexual sporulation defects of cfwA, fluG and tmpA mutants were not rescued by the cfwA-dependent compounds identified here. However, cfwA2 mutation enhanced the sporulation defects of both tmpA and fluG single mutants, suggesting that unidentified CfwA-dependent PKS and/or NRPS are involved in the production of hitherto unknown compounds, required for sporulation. Our results expand the number of known and predicted secondary metabolites requiring CfwA/NpgA for their biosynthesis, and together with the phylogenetic analysis of fungal PPTases suggest that a single PPTase is responsible for activation of all PKSs and NRPSs in A. nidulans.

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