Aspergillus/Aspergillosis Website

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MIGUEL A. PEÑALVA BSc PhD

Professor Penalva graduated in Biology from the University Complutense de Madrid in 1978. His Phd was completed in 1982 at the Universidad Autónoma de Madrid, supervised by Prof. Margarita Salas.

After a period of time working on DNA synthesis and replication in bacteriophage f29 he acquired and interest in the molecular genetics of Aspergillus and other fungi, cloning and characterising the trpC gene in; Penicillium chrysogenum, the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans, pyr4 gene in Cephalosporium acremonium, the uaY regulatory gene of A. nidulans.

He has gone on to make several important contributions to transcriptional regulation of antibiotic synthesis in Aspergillus amd others. A summary of the work currently underway in his laboratory can be found at the Departamento de Microbiología Molecular Genética, Molecular de Aspergillus website.

Awards and Memberships

1987. Boehringer Award, Sociedad Española de Bioquímica
1996, 2003- Member of the “Biology and Biomedicine Committee” Spanish Research Council, CSIC
1998-2002 Executive Secretary of the Spanish Biotechnology Funding Program, DGICYT
2000- EMBO member

Representative publications

Books

M.A. Peñalva, A. Vian, C. Patiño, A. Pérez y D. Ramón. Molecular Biology of Penicillin Production in Aspergillus nidulans. En Genetics and Molecular Biology of Industrial Microorganisms. Eds.: C.L. Hershberger, S.W. Queener y G. Hegeman. American Society for Microbiology. Washington D.C., p. 256-261 (1990).

M.A. Peñalva, E. Espeso, M. Orejas y E. Gómez-Pardo. Evolution and control of gene expression of the Aspergillus nidulans isopenicillin N synthetase gene. En Proceedings of the Symposium " 50 Years of Penicillin Application". H. Kleinkauf y H. Van Doren (Eds.). Berlín, 1990.

M.A. Peñalva, B. Pérez-Esteban, E. Gómez-Pardo, M. Orejas, M. y E. Espeso . Penicillin production by Aspergillus nidulans: studies on the regulation of expression of the IPNS gene. In "Molecular Biology of Filamentous Fungi" (Tudzynski, P. and Stahl, U., eds.). VGH, Weinheim, FRG, pp. 217-228 (1991).

J.M. Luengo and M. A. Peñalva. Penicillin biosynthesis. En "Aspergillus: 50 years on". S. D. Martinelli and J. R. Kinghorn (Eds.). Elsevier, Amsterdam, London, pp. 603-638 (1994) .

Representative publications

M.A. Peñalva and M. Salas. Initiation of phage f29 DNA replication in vitro: formation of a covalent complex between the terminal protein, p3, and 5'-dAMP. Proc. Natl. Acad. Sci. USA 79, 5522-5526 (1982).

J.A. García, M.A. Peñalva, L. Blanco, and M. Salas. Template requirements for initiation of phage f29 DNA replication in vitro. Proc. Natl. Acad. Sci. USA 81, 80-84 (1984).

F. Sánchez, A. Touriño, S. Traseira, A. Pérez, V. Rubio y M.A. Peñalva. Molecular cloning and characterization of the trpC gene from Penicillium chrysogenum. Mol. Gen. Genet. 205, 248-252 (1986).

D. Ramón, L. Carramolino, C. Patiño, F. Sánchez y M.A. Peñalva. Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans. Gene 57, 171-181 (1987).

A. Vian and M.A. Peñalva. Cloning of the pyr4 gene encoding orotidine-5'-phosphate decarboxylase in Cephalosporium acremonium. Current Genetics 17, 223-227 (1990).

Peñalva, M.A., Espeso, E., Pérez-Esteban, B., Orejas, M., Fernández-Cañón, J.M. and Martínez-Blanco, H. Expression of fungal genes involved in penicillin biosynthesis. World J. Biotechnol. 9: 461-467 (1993).

B. Pérez-Esteban, M. Orejas, E. Gómez-Pardo and M.A. Peñalva. Molecular characterisation of a fungal secondary metabolism promoter: transcription of the Aspergillus nidulans isopenicillin N synthetase gene is modulated by upstream negative elements. Mol. Microbiol. 9: 881-895 (1993).

Espeso, E.A., Tilburn, J., Arst, H.N., Jr. and Peñalva, M.A. pH regulation is a major determinant in expression of a fungal penicillin biosynthetic gene. EMBO J. 12: 3947-3956 (1993).

Fernández-Cañón, J.M. and Peñalva, M.A. Overexpression of two penicillin structural genes in Aspergillus nidulans. Mol. Gen. Genet. 246: 110-118 (1995).

Tilburn, J., S. Sarkar, D.A. Widdick, E.A. Espeso, M. Orejas, J. Mungroo, M.A. Peñalva, and H.N. Arst, Jr. The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J. 14: 779-790 (1995).

Fernández-Cañón, J.M. and Peñalva, M.A. Fungal metabolic model for type I hereditary tyrosinaemia. Proc. Natl. Acad. Sci. USA 92: 9132-9136 (1995).

Orejas, M., Espeso, E., Tilburn, J., Sarkar, S., Arst, H.N., Jr. and Peñalva, M.A. Activation of the Aspergillus PacC transcription factor in response to alkaline ambient pH requires proteolysis of the carboxy-terminal moiety Genes & Devel. 9: 1622-1632 (1995).

Fernández-Cañón, J.M and Peñalva, M.A. Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues. J. Biol. Chem. 270, 21199-21205 (1995).

Fernández-Cañón, J.M., Granadino, B., Beltrán-Valero, D., Renedo, M., Fernández-Ruiz, M., Peñalva, M.A. and Rodríguez de Córdoba, S.The molecular basis of alkaptonuria. Nature Genetics 14: 19-24 (1996).

Espeso, E.A. and Peñalva, M.A. Three binding sites for the Aspergillus nidulans PacC-zinc finger transcription factor are neccesary and sufficient for regulation by ambient pH of the Aspergillus nidulans isopenicillin N synthase gene promoter. J. Biol. Chem. 271: 28825-28830 (1996) .

Espeso, E.A., Tilburn, J., Sánchez-Pulido, L., Brown, C.V., Valencia, A., Arst, H.N., Jr. and Peñalva, M.A. Specific DNA recognition by the Aspergillus nidulans three zinc finger transcription factor PacC. J. Mol. Biol. 274: 466-480 (1997).

Fernández-Cañón, J.M. and Peñalva, M.A. Characterization of a fungal maleylacetoacetate isomerase gene and identification of its human homologue. J. Biol. Chem. 273: 329-337 (1998).

Reoyo, E., Espeso, E.A., Peñalva, M.A. and Suárez, T. The essential Aspergillus nidulans gene pmaA encodes an homologue of fungal plasma membrane H⁺-ATPases. Fungal Genet. Biol. 23: 288-299 (1998).

Denison, S.H., Negrete-Urtasun, S., Mingot, J.-M., Tilburn, J., Mayer, W.A., Goel,A., Espeso, E.A., Peñalva, M.A., and Arst, H.N.,Jr. Putative membrane components of signal transduction pathways for ambient pH regulation in Aspergillus and meiosis in Saccharomyces are homologous. Mol. Microbiol. 30: 259-264 (1998) .

Peñalva, M.A., Rowlands, R. and Turner, G.T. The optimization of penicillin biosynthesis in fungi. Trends in Biotechnology 16, 483-489 (1998).

J.-M. Mingot, J. Tilburn, E. Díez, E. Bignell, M. Orejas, D.A. Widdick, S. Sarkar, C.V. Brown, M.X. Caddick, E.A. Espeso, H.N. Arst, Jr. and M.A. Peñalva. Specificity determinants of proteolytic processing of the Aspergillus PacC transcription factor are remote from the processing site and processing occurs in yeast provided pH signalling is bypassed. Mol. Cell. Biol. 19: 1390-1400 (1999).

Mingot, J.M., Peñalva, M.A. and Fernández-Cañón, J.M. Disruption of phacA, and Aspergillus nidulans gene encoding a novel cytochrome P450 monooxygenase catalyzing phenylacetate 2-hydroxylation, results in penicillin overproduction. J. Biol. Chem. 274:14545-14550 (1999).

Negrete-Urtasun, S., Reiter, W. , Díez, E., Denison, S.H., Tilburn, J., Espeso, E.A., Peñalva, M.A. and Arst. H.N., Jr. Ambient pH signal transduction in Aspergillus: completion of gene characterisation. Mol. Microbiol. 33: 994-1003 (1999).

E.A. Espeso, T. Roncal, E. Díez, L. Rainbow, E. Bignell, J. Álvaro, T. Suárez, S.H. Denison, J. Tilburn, H.N. Arst, Jr. and M.A. Peñalva. On how a transcription factor can avoid its proteolytic activation in the absence of signal transduction. EMBO J. 19: 719-728 (2000).

J.M. Mingot, E.A. Espeso, E. Díez and M.A. Peñalva (2001) Ambient pH signaling regulates nuclear localization of the Aspergillus nidulans PacC transcription factor. Mol. Cell. Biol. 21: 1688-1699.

M. A. Peñalva. (2001) A fungal perspective on human inborn errors of metabolism: alkaptonuria and beyond. Fungal.Genet.Biol. 34:1-10.

Díez, E., Álvaro, J., Espeso, E.A., Rainbow, L., Suárez, T., Tilburn, J., Arst, H.N., Jr. and Peñalva, M.A. (2002) Activation of the Aspergillus PacC zinc-finger transcription factor requires two proteolytic steps. EMBO J. 21: 1350-1359.

Peñalva, M.A. and Arst, H.N., Jr. (2002) Regulation of Gene Expression by Ambient pH in Filamentous Fungi and Yeasts. Microbiol. Mol. Biol. Reviews 66: 426-446.

Vincent, O., Rainbow, L., Tilburn, J., Arst, H. N., Jr. and Peñalva, M. A. (2003) YPXL/I is a protein interaction motif recognized by Aspergillus PalA and its human homologue AIP1/Alix. Mol. Cell. Biol. 23(5): 1647-1655.

Arst, H.N., Jr. And Peñalva, M. A. (2003) pH regulation in Aspergillus and parallels with higher eukaryotic regulatory systems. Trends in Genetics 19: 224-231.

Rodríguez,J.M., Ruíz-Sala,P., Ugarte,M. and Peñalva,M.A. (2004) Fungal metabolic model for 3-methylcrotonyl-CoA carboxylase deficiency. J. Biol. Chem. 279: 4578-4587.

Peñalva MA, and Arst HN Jr. (2004) Recent advances in the characterization of ambient pH regulation of gene expression in filamentous fungi and yeasts Annu Rev Microbiol 4; 58.

J. M. Rodríguez, P. Ruiz-Sala, M. Ugarte, and M. A. Peñalva (2004). Fungal Metabolic Model for Type I 3-Methylglutaconic Aciduria. J.Biol.Chem. 279:32385-32392.

Tilburn J, Sanchez-Ferrero JC, Reoyo E, Arst HN Jr, Penalva MA. Mutational analysis of the pH signal transduction component PalC of Aspergillus nidulans supports distant similarity to BRO1 domain family members. Genetics. 2005 Sep;171(1):393-401.

Herranz S, Rodriguez JM, Bussink HJ, Sanchez-Ferrero JC, Arst HN Jr, Penalva MA, Vincent O. Arrestin-related proteins mediate pH signaling in fungi. Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12141-6.

Tracing the endocytic pathway of Aspergillus nidulans with FM4-64. Fungal Genet Biol. 2005 Dec;42(12):963-75.

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