Aharonowitz Y, Cohen G, Martín JF (1992) Penicillin and cephalosporin biosynthetic genes: structure, organization, regulation and evolution. Annu Rev Microbiol 46:461–495

Article  PubMed  CAS  Google Scholar 

Andrade AC, Del Sorbo G, Van Nistelrooy JG, Waard MA (2000) The ABC transporter AtrB from Aspergillus nidulans mediates resistance to all major classes of fungicides and some natural toxic compounds. Microbiology 146:1987–1997

PubMed  CAS  Google Scholar 

Brakhage AA (1998) Molecular regulation of beta-lactam biosynthesis in filamentous fungi. Microbiol Mol Biol Rev 62:547–585

PubMed  CAS  Google Scholar 

Cantoral JM, Díez B, Barredo JL, Alvarez E, Martín JF (1987) High-frequency transformation of Penicillium chrysogenum. Biotechnology 5:494–497

Article  CAS  Google Scholar 

Cantoral JM, Gutiérrez S, Fierro F, Gil-Espinosa S, van Liempt H, Martín JF (1993) Biochemical and characterization and molecular genetics of nine mutants of Penicillium chrysogenum impaired in penicillin biosynthesis. J Biol Chem 268:737–744

PubMed  CAS  Google Scholar 

Cantwell C, Beckmann R, Whiteman P, Queener SW, Abraham EP (1992) Isolation of deacetoxycephalosporin C from fermentation broths of Penicillium chrysogenum transformants: construction of a new fungal biosynthetic pathway. Proc R Soc Lond B 248:283–289

Article  CAS  Google Scholar 

Casqueiro J, Bañuelos O, Gutiérrez S, Hijarrubia MJ, Martín JF (1999a) Intrachromosomal recombination in Penicillium chrysogenum: gene conversion and deletion events. Mol Gen Genet 261:994–1000

Article  PubMed  CAS  Google Scholar 

Casqueiro J, Gutiérrez S, Bañuelos O, Hijarrubia MJ, Martín JF (1999b) Gene targeting in Penicillium chrysogenum: disruption of the lys2 gene leads to penicillin overproduction. J Bacteriol 181:1181–1188

PubMed  CAS  Google Scholar 

Crawford L, Stepan AM, McAda PC, Rambonsek JA, Conder MJ, Vinci VA, Reeves CD (1995) Production of cephalosporin intermediates by feeding adipic acid to recombinant Penicillium chrysogenum strains expressing ring activity. Biotechnology 13:58–62

Article  PubMed  CAS  Google Scholar 

Demain AL, Elander RP (1999) The beta-lactam antibiotics: past, present, and future. Antonie Van Leeuwenhoek 75:5–19

Article  PubMed  CAS  Google Scholar 

Demain AL, Zhang J (1998) Cephalosporin C production by Cephalosporium acremonium: the methionine story. Crit Rev Biotechnol 18:283–294

Article  PubMed  CAS  Google Scholar 

Díez B, Alvarez E, Cantoral JM, Barredo JL, Martín JF (1987) Isolation and characterization of pyrG mutants of Penicillium chrysogenum by resistance to 5′-fluoroorotic acid. Curr Genet 12:277–282

Article  Google Scholar 

Díez B, Mellado E, Rodríguez M, Fouces R, Barredo JL (1997) Recombinant microorganisms for industrial production of antibiotics. Biotechnol Bioeng 55:216–226

Article  PubMed  Google Scholar 

Drew SW, Demain AL (1973) Methionine control of cephalosporin C formation. Biotechnol Bioeng 15:743–754

Article  PubMed  CAS  Google Scholar 

Elander RP (2003) Industrial production of beta-lactam antibiotics. Appl Microbiol Biotechnol 61:385–392

PubMed  CAS  Google Scholar 

Fernández FJ, Gutiérrez S, Velasco J, Montenegro E, Marcos AT, Martín JF (1994) Molecular characterization of three loss-of-function mutations in the isopenicillin N acyltransferase gene (penDE) of Penicillium chrysogenum. J Bacteriol 176:4941–4948

PubMed  Google Scholar 

Fierro F, Gutiérrez S, Díez B, Martín JF (1993) Resolution of four chromosomes in penicillin-producing filamentous fungi: the penicillin gene cluster is located on chromosome II (9.6 Mb) in Penicillium notatum and chromosome I (10.4 Mb) in Penicillium chrysogenum. Mol Gen Genet 241:573–578

Article  PubMed  CAS  Google Scholar 

Fierro F, Barredo JL, Díez B, Gutiérrez S, Fernández FJ, Martín JF (1995) The penicillin gene cluster is amplified in tandem repeats linked by conserved hexanucleotide sequences. Proc Natl Acad Sci USA 92:6200–6204

Article  PubMed  CAS  Google Scholar 

Fierro F, Montenegro E, Gutiérrez S, Martín JF (1996) Mutants blocked in penicillin biosynthesis show a deletion of the entire penicillin gene cluster at a specific site within a conserved hexanucleotide sequence. Appl Microbiol Biotechnol 44:597–604

Article  PubMed  CAS  Google Scholar 

García-Estrada C, Vaca I, Lamas-Maceiras M, Martín JF (2007) In vivo transport of the intermediates of the penicillin biosynthetic pathway in tailored strains of Penicillium chrysogenum. Appl Microbiol Biotechnol 76:169–182

Article  PubMed  Google Scholar 

Gutiérrez S, Díez B, Álvarez E, Barredo JL, Martín JF (1991) Expression of the penDE gene of Penicillium chrysogenum encoding isopenicillin N acyltransferase in Cephalosporium acremonium: production of benzylpenicillin by the transformants. Mol Gen Genet 225:56–64

Article  PubMed  Google Scholar 

Komatsu KI, Mizuno M, Kodaira R (1975) Effect of methionine on cephalosporin C and penicillin N production by a mutant of Cephalosporium acremonium. J Antibiot 28:881–888

PubMed  CAS  Google Scholar 

Le Page GA, Campbell E (1946) Preparation of streptomycin. J Biol Chem 162:163–171

CAS  Google Scholar 

Liras P, Martín JF (2006) Gene clusters for β-lactam antibiotics and control of their expression: why have clusters been formed and where do they come from? Int Microbiol 9:9–19

PubMed  CAS  Google Scholar 

Martín JF, Demain AL (2002) Unraveling the methionine-cephalosporin puzzle in Acremonium chrysogenum. Trends Biotechnol 20:502–507

Article  PubMed  Google Scholar 

Martín JF, Ullán RV, Casqueiro J (2004) Novel genes involved in cephalosporin biosynthesis: the three-component isopenicillin N epimerase system. Adv Biochem Eng Biotechnol 88:91–109

PubMed  Google Scholar 

Martín JF, Casqueiro J, Liras P (2005) Secretion systems for secondary metabolites: how producer cells send out messages of intercellular communication. Curr Opin Microbiol 8:282–293

Article  PubMed  Google Scholar 

Nijland JG, Evers ME, Driessen AJM (2005) The isolation and identification of a cephalosporin transporter homologue in Penicillium chrysogenum. Fungal Genetics Newsletter, 52-Supplement. XXIII-Fungal Genetics Conference. Cell Biology 42, pp 50

Rodríguez-Sáiz M, Lembo M, Bertetti L, Muraca R, Velasco J, Malcangi A, de la Fuente JL, Barredo JL (2004) Strain improvement for cephalosporin production by Acremonium chrysogenum using geneticin as a suitable transformation marker. FEMS Microbiol Lett 235:43–49

Article  PubMed  Google Scholar 

Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

Google Scholar 

Shen YQ, Wolfe S, Demain AL (1986) Levels of isopenicillin N synthetase and deacetoxycephalosporin C synthetase in Cephalosporium acremonium producing high and low levels of cephalosporin C. Biotechnology 4:61–64

Article  CAS  Google Scholar 

Ullán RV, Liu G, Casqueiro J, Gutiérrez S, Bañuelos O, Martín JF (2002a) The cefT gene of Acremonium chrysogenum C10 encodes a putative multidrug efflux pump protein that significantly increases cephalosporin C production. Mol Genet Genomics 267:673–683

Article  PubMed  Google Scholar 

Ullán RV, Casqueiro J, Bañuelos O, Fernández FJ, Gutiérrez S, Martín JF (2002b) A novel epimerization system in fungal secondary metabolism involved in the conversion of isopenicillin N into penicillin N in Acremonium chrysogenum. J Biol Chem 277:46216–46225

Article  PubMed  Google Scholar 

Ullán RV, Casqueiro J, Naranjo L, Vaca I, Martín JF (2004) Expression of cefD2 and the conversion of isopenicillin N into penicillin N by the two-component epimerase system are rate-limiting steps in cephalosporin biosynthesis. Mol Genet Genomics 272:562–570

Article  PubMed  Google Scholar 

Ullán RV, Campoy S, Casqueiro J, Fernández FJ, Martín JF (2007) Deacetylcephalosporin C production in Penicillium chrysogenum by expression of the isopenicillin N epimerization, ring expansion, and acetylation genes. Chem Biol 14:329–339

Article  PubMed  Google Scholar 

Ullán RV, Godio RP, Teijeira F, Vaca, I, García-Estrada C, Feltrer R, Kosalková K, Martín JF (2008) RNA-silencing in Penicillium chrysogenum and Acremonium chrysogenum: validation studies using β-lactam genes expression. J Microbiol Methods (in press)

Velasco J, Gutierrez S, Fernandez FJ, Marcos AT, Arenos C, Martin JF (1994) Exogenous methionine increases levels of mRNAs transcribed from pcbAB, pcbC, and cefEF genes, encoding enzymes of the cephalosporin biosynthetic pathway, in Acremonium chrysogenum. J Bacteriol 176:985–991

PubMed  CAS  Google Scholar 

Velasco J, Gutiérrez S, Casqueiro J, Fierro F, Campoy S, Martín JF (2001) Cloning and characterization of the gene cahB encoding a cephalosporin C acetylhydrolase from Acremonium chrysogenum. Appl Microbiol Biotechnol 57:300–356

Google Scholar