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Eukaryotic Cell, April 2007, p. 710-720, Vol. 6, No. 4
1535-9778/07/$08.00+0     doi:10.1128/EC.00362-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Phosphopantetheinyl Transferase CfwA/NpgA Is Required for Aspergillus nidulans Secondary Metabolism and Asexual Development{triangledown} ,{dagger}

Olivia Márquez-Fernández,1,2 Ángel Trigos,1,2 Jose Luis Ramos-Balderas,3 Gustavo Viniegra-González,4 Holger B. Deising,5 and Jesús Aguirre3*

Instituto de Ciencias Básicas, Universidad Veracruzana, Av. Dos Vistas s/n, Carretera Xalapa-Las Trancas, 91000 Veracruz, Xalapa, México,1 Laboratorio de Alta Tecnología, Médicos No. 5, Unidad del Bosque, Veracruz, Xalapa, México,2 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, 04510 México D.F., México,3 Departamento de Biotecnología, Universidad Autónoma Metropolitana, Av. Michoacán y La Purísima, 09340 México D.F., México,4 Martin Luther University Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Phytopathology, and Plant Protection, Ludwig Wucherer Str. 2, D-06099 Halle (Saale), Germany5

Received 16 November 2006/ Accepted 25 January 2007

Polyketide synthases (PKSs) and/or nonribosomal 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 ({Delta}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 the production of these polyketide compounds but dispensable for ergosterol and cerevisterol and for fatty acid biosynthesis. The asexual sporulation defects of cfwA, {Delta}fluG, and {Delta}tmpA mutants were not rescued by the cfwA-dependent compounds identified here. However, a cfwA2 mutation enhanced the sporulation defects of both {Delta}tmpA and {Delta}fluG single mutants, suggesting that unidentified CfwA-dependent PKSs and/or NRPSs 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 the activation of all PKSs and NRPSs in A. nidulans.

* Corresponding author. Mailing address: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, 04510 México D.F., México. Phone: (5255) 5622 5651. Fax: (5255) 5622 5630. E-mail: jaguirre{at}ifc.unam.mx

{triangledown} Published ahead of print on 2 February 2007.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, April 2007, p. 710-720, Vol. 6, No. 4
1535-9778/07/$08.00+0     doi:10.1128/EC.00362-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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