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Microbial APIs production

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Microbial APIs production

Microorganisms are main producers of Active Pharmacological ingredients (APIs). Inbiotec is leading since its inception the research in this field, laying the groundwork and developing the innovations which have enabled new and improved industrial processes to achieve better and more affordable medications, from antimicrobials that fight against infectious diseases to immunotherapics enabling organ transplants.

Related projects:

2016 MySterI: Novel industrial bioprocesses for production of key valuable steroid precursors from phytosterol (EIB.12.010) ERA-IB-FP7 (05/12/2013-30/11/2016)
2016 SCILS: Systematic consideration of inhomogeneity at the large scale: towards a stringent development of industrial bioprocesses (EIB.12.057) ERA-IB-FP7 (05/12/2013-30/11/2016)
2014 IMMUNOTEC: Robust fermentation production of tacrolimus and related immunosuppressors: Molecular genetics and metabolic engineering to construct a by-product free superproducer.ERA-IB-FP7: (2011-2014)
2013 BIO2010-19911 (01/01/2011-31/12/2013) Estrategias de regulación de la biosíntesis de macrólidos antifúngicos (REBIMA).
2012 BIO2009-09820 (01/01/2010-31/12/2012). Análisis funcional de las agrupaciones génicas para metabolitos secundarios en Streptomyces clavuligerus (METABOCLAV).
2012 CCTT/10/LE/0001-B3 (01/01/2010-31/03/2012). “Inteligencia artificial y bioinformática para la optimización de la producción deinmunosupresores-Fase I (BIOPAC)”.
2012 CCTT/10/LE/001. (01/01/2010-31/03/2012). “Inteligencia artificial y bioinformática para la optimización de la producción de inmunosupresores-Fase I”. Agencia de Innovación y Financiación Empresarial (ADE). Junta de Castilla y León. Modalidad: En Cooperación.
2012 PROYECTO GENÉRICO DE DESARROLLO TECNOLÓGICO (2009). AGENCIA DE INVERSIONES Y SERVICIOS DE CASTILLA Y LEÓN. Optimización en planta piloto de la producción del antitumoral Geldanamicina utilizando cepas modificadas genéticamente (ya obtenidas) y otras de nuevo diseño.
2011 BIO2006-14853-C02-01 (CONSOLIDER) (12/2006-11/2011). “Control de la biosíntesis de metabolitos secundarios por el reguladorphoP mediante cascadas de proteínas fosforiladas enStreptomyces coelicolor (actinomiceto modelo): Aplicación a la eliminación del control por fosfato de la biosíntesis del inmunosupresor tacrolimus en Streptomyces sp ATCC 55098”.
2011 PROYECTO GENÉRICO DE DESARROLLO TECNOLÓGICO (2008). AGENCIA DE INVERSIONES Y SERVICIOS DE CASTILLA Y LEÓN. “Eliminación de etapas limitantes en la producción de cefalosporinas en Planta Piloto mediante el aumento de la transferencia de oxígeno en los fermentadores”.
2011 PROYECTO GENÉRICO DE DESARROLLO TECNOLÓGICO (2008). AGENCIA DE INVERSIONES Y SERVICIOS DE CASTILLA Y LEÓN. “Supreproducción del anticancerígeno Geldanamicina mediante modificación genética de las cepas productoras”.
2010 SYSMO GEN: Global metabolic switching in Streptomyces coelicolor.2006-27745-E/SYS (01/03/2007-28/02/2010).
2010 BIO2007-67585 (01/10/2007-04/10/2010). “Mecanismos comunes de regulación de la producción de macrólidos polienos”.
2010 IAP-580000-2008-42 (04/05/2009-30/06/2010). “Obtención de cepas superproductoras de colesterol oxidasa. Estudios en planta piloto”.
2010 Grupos de excelencia investigadora de Castilla y León (GR117). Junta de Castilla y León (01/01/2008-31/10/2010). Biología de la producción de metabolitos bioactivos en especies de Streptomyces.
2009 ACTINOGEN: Integrating Genomics-Based applications to exploit Actinomycetes as a resource for new antibiotics. FP6. LSHM-CT-2004-005224 (01/01/2005-31/12/2009)
2009 BIO2006-14853-C02-02. (12/2006-11/2009). “Estudio genómico y proteómico de S. clavuligerus en relación a la producción de ácido clavulanico, cefamicina C y otros metabolitos secundarios”.
2009 IAP-580000-2008-50 (05/2008-31/12/2009). “Produccion biotecnológica de los inmunosupresores sirolimus y pimecrolimus”. Modalidad: En Cooperación. Coordinador: ANTIBIOTICOS, S.A., Participante: INBIOTEC.Financiación: Ministerio Industria Turismo y Comercio. Convocatoria de Industria (Empresas).
2009 PID-580000-2009-3. (04/05/09-21/12/09). Obtención de cepas superproductoras de colesterol oxidasa: Estudios en planta piloto. Financiación: Ministerio de Ciencia e Innovación. Subprograma Centros tecnológicos.
2008 PROFIT: FIT-010000-2007-76. (01/01/2007-30/06/2008). “Optimización de la producción de Geldanamicina y optimización de las condiciones de fermentación y extracción del producto. Modalidad: En Cooperación. Coordinador: Instituto Biomar S.A., Participante: INBIOTEC. Financiación: Ministerio Industria Turismo y Comercio. Convocatoria de Industria (Empresas)
2008 PROFIT: FIT-010000-2007-57. (01/01/2007-30/06/2008). “Producción biotecnológica de los inmunosupresores sirolimus y pimecrolimus”. Modalidad: En Cooperación. Coordinador: ANTIBIOTICOS, S.A., Participante: INBIOTEC. Financiación: Ministerio Industria Turismo y Comercio. Convocatoria de Industria (Empresas).
2008 PROFIT: FIT-010000-2007-74. (01/01/2007-30/06/2008). “Modelización de procesos para la producción biotecnológica”. Modalidad: En Cooperación. Coordinador: ANÁLISIS DSC., Participante: INBIOTEC. Financiación: Ministerio Industria Turismo y Comercio. Convocatoria de Industria (Empresas).
2007 BIO2004-00066 (11/12/2004-11/12/2007). “Modulación de la biosíntesis del antifúngico Pimaricina como modelo para la producción de macrólidos polienos”
2006 PROFIT: FIT-010000-2006-9. (01/01/2006-31/12/2006). “Producción biotecnológica de los inmunosupresores tacrolimus, sirolimus y pimecrolimus”. Modalidad: En Cooperación. Coordinador: Antibióticos S.A., Participante: INBIOTEC.
2006 PROYECTO GENÉRICO DE DESARROLLO TECNOLÓGICO (2003). AGENCIA DE DESARROLLO ECONÓMICO. JUNTA DE CASTILLA Y LEÓN. “Optimización en Planta Piloto de las cepas superproductoras de renina (quimosina) bovina y de cefalosporinas (1º fase).
2005 PROFIT FIT-010000-2002-165. (2002). “Efecto del gen regulador FADA de Penicillium chrysogenum sobre la biosíntesis de Penicilina. Obtención de cepas superproductoras de este gen”.
2005 FUNDACIÓN RAMÓN ARECES (07/2002-06/2005). “Análisis genómico y proteómico comparativo de Streptomyces clavuligerus, productor de ácido clavulánico, y del organismo modeloStreptomyces coelicolor”. I.P: Dra. Paloma Liras Padín.
2005 PROFIT: FIT-010000-2004-228 (01/2004-06/2005). “Alteración del gen regulador FADA de Penicillium chrysogenum sobre la biosíntesis de penicilinas. Obtención de cepas superproductoras por modificación de este gen”.
2005 PROYECTO GENÉRICO DE DESARROLLO TECNOLÓGICO (2002). AGENCIA DE DESARROLLO ECONÓMICO. JUNTA DE CASTILLA Y LEÓN. “Producción en Planta Piloto de proteínas y metabolitos en bacterias y hongos filamentosos.” (2º fase).
2004 STREPSEC: Explotation of Streptomyces protein secretion for robust biopharmaceutical bioprocess development. FP5.QLRT-2000-00122 (04/2001-03/2004)
2004 BIO2001-0040 (12/2001-12/2004). “Ingeniería de nuevos macrólidos antifúngicos: Pimaricinas híbridas e inductores”.
2004 BIO2001-0060-P4-03 (11/2001-11/2004). “Optimización de la producción de cefalosporinas mediante modificación de los genes biosintéticos y reguladores y la obtención de 7-ACA mediante conversión enzimática utilizando D-aminoácido oxidasa y glutaril-acilasa”.
2004 PROFIT FIT-010000-2001-130. (2001). “Investigación y desarrollo de procesos para la producción industrial de Penicilina”.
2004 PROFIT FIT-010000-2003-113 (01/2003-06/2004). “Efecto del gen regulador FADA de Penicillium chrysogenum sobre la biosíntesis de Penicilina. Obtención de cepas superproductoras de este gen”.
2004 PROYECTO GENÉRICO DE DESARROLLO TECNOLÓGICO (2001). AGENCIA DE DESARROLLO ECONÓMICO. JUNTA DE CASTILLA Y LEÓN. “Sobreproducción de proteínas y metabolitos en hongos filamentosos.
2003 BIO2000-0272 (12/2000-12/2003). “Modulación de la producción de ácido clavulánico y cefamicina C mediante la modificación de las proteínas ribosomales de Streptomyces clavuligerus”.
2003 FUNDACIÓN RAMÓN ARECES (03/2000-02/2003). “Mecanismo molecular del control por fosfato de la producción del antifúngico pimaricina en Streptomyces natalensis: Cepas alteradas en el control por fosfato”. I.P. Dr. Juan Francisco Martín Martín.
2001 1FD97-0224-C03-02 (11/1998-10/2001). “Mejora de la producción de pigmentos y lovastatina por modificación genética de Monascus.”
2001 1FD97-1419-C02-01 (12/1999-12/2001). “Regulación de la producción de pimaricina en Streptomyces natalensis: Aplicación en la producción industrial de este agente antifúngico”.
2000 Characterization of the secretory pathway of Streptomyces lividans and its modification for the overproduction of heterologous proteins. FP4-Biotech 2. (09/1998-11/2000).
2000 BIO97-0289-C02-01.”Ingeniería metabólica de la síntesis de péptidos no-ribosomales: Canalización del flujo de lisina y valina hacia derivados de estos aminoácidos. Aplicación a la superproducción de cefalosporinas”.

Related publications:

2016 Rodríguez-García A, Fernández-Alegre E, Morales A, Sola-Landa A, Lorraine J, Macdonald S, Dovbnya D, Smith MC, Donova M, Barreiro C. Complete genome sequence of ‘Mycobacterium neoaurum’ NRRL B-3805, an androstenedione (AD) producer for industrial biotransformation of sterols. J Biotechnol. 2016 Mar; 224:64-65. doi:10.1016/j.jbiotec.2016.03.021. PMID: 26988397
2016 Barreiro C*, Ullán RV. DNA-synthesizing enzymes as antibacterial targets (Chapter 4). 2016. In: New weapons to control bacterial growth. Editor: Tomás G. Villa y Miguel Viñas. Springer International Publishing. Hardcover ISBN: 978-3-319-28366-1. (*Corresponding author).
2016 Ullán RV, Barreiro C. Bacterial protease as targets to control bacterial growth (Capítulo 6). 2016. En: New weapons to control bacterial growth. Editor: Tomás G. Villa y Miguel Viñas. Editorial: Springer International Publishing. Hardcover ISBN: 978-3-319-28366-1.
2015 Martínez-Burgo Y, Álvarez-Álvarez R, Rodríguez-García A, Liras P. The Pathway-Specific Regulator ClaR of Streptomyces clavuligerus Has a Global Effect on the Expression of Genes for Secondary Metabolism and Differentiation. Appl Environ Microbiol. 2015 Oct;81(19):6637-48. doi:10.1128/AEM.00916-15.PMID: 26187955
2015 ZEILINGER S., GARCÍA-ESTRADA C., MARTÍN J.F. (2015). Fungal secondary metabolites in the “OMICS” era. In Biosynthesis and molecular genetics of fungal secondary metabolites Vol II. (eds. S Zeilinger, J.F. Martín, C. García-Estrada and). Springer US, New York, NY 10013, USA., pp. 1-12. ISBN 978-1-4939-2530-8.
2015 GARCÍA-ESTRADA C., ULLÁN R.V. (2015). RNAi-mediated gene silencing in the beta-lactam producer fungi Penicillium chrysogenum and Acremonium chrysogenum. In Genetic Transformation Systems in Fungi, Vol. 2 (eds. M.A. Van den Berg and K. Maruthachalam). Springer International Publishing, Switzerland, pp.125-130. ISBN 978-3-319-10502-4.
2015 Domínguez-Santos R, García-Estrada C, Kosalková K, Prieto C, Santamarta I, Martín JF. PcFKH1, a novel regulatory factor from the forkhead family, controls the biosynthesis of penicillin in Penicillium chrysogenum. Biochimie. 2015;115:162-76. Epub 2015 Jun 4. 26049046.
2015 Barreiro C (Ed, preface). New trends in Corynebacterium glutamicum: beyond the amino acids. 2015. , Nova Science Publishers (New York, USA). ISBN: 978-1-63483-280-9.
2015 Barreiro C. Methods in Proteomics applied to Corynebacterium glutamicum. 2015., New trends in Corynebacterium glutamicum: beyond the amino acids.Nova Science Publishers (New York, USA). ISBN: 978-1-63483-280-9.
2015 Pérez-Redondo, R.; Sola-Landa, A. & Rodríguez-García, A.Barreiro, C., ed., (2015), New Trends in Corynebacterium glutamicum: Beyond the Amino Acids., Nova Science Publishers, New York, chapter Chapter 2: Deciphering the Dynamic Transcriptome Employing Microarrays., pp. 13–44. (Book chapter)
2014 Balaña-Fouce R, Alvarez-Velilla R, Fernández-Prada C, García-Estrada C, Reguera RM. Trypanosomatids topoisomerase re-visited. New structural findings and role in drug discovery. Int J Parasitol Drugs Drug Resist. 2014 Aug 24;4(3):326-37. doi: 10.1016/j.ijpddr.2014.07.006. eCollection 2014 Dec. Review. 25516844.
2014 Cepeda-García C, Domínguez-Santos R, García-Rico RO, García-Estrada C, Cajiao A, Fierro F, Martín JF. Direct involvement of the CreA transcription factor in penicillin biosynthesis and expression of the pcbAB gene in Penicillium chrysogenum. Appl Microbiol Biotechnol. 2014 Aug;98(16):7113-24. Epub 2014 May 13. 24818689.
2014 GARCÍA-ESTRADA C., MARTÍN J.F. (2014) Penicillins. In Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites Vol. I (eds. C. García-Estrada, S Zeilinger and J.F. Martín). Springer US, New York, NY 10013, USA., pp. 17-42. ISBN 978-1-4939-1190-5.
2014 DOMÍNGUEZ-SANTOS R., MARTÍN J.F., GARCÍA-ESTRADA C. (2013) Regulatory Processes Controlling the Biosynthesis of Beta-lactam Antibiotics in Penicillium chrysogenum and Acremonium chrysogenum. In Recent Developments in Biotechnology (Drug Discovery) Vol. 9 (ed. V.K. Govil). Studium Press LLC, Houston, Texas 77072, USA., Chapter 7, pp. 225-262. ISBN 1-62699-022-0.
2014 Fernández-Aguado M, Martín JF, Rodríguez-Castro R, García-Estrada C, Albillos SM, Teijeira F, Ullán RV. New insights into the isopenicillin N transport in Penicillium chrysogenum. Metab Eng. 22: 89-103. Mar 2014. 24480587
2014 Salehi-Najafabadi Z, Barreiro C, Rodríguez-García A, Cruz A, López G E & Martín J F The gamma-butyrolactone receptors BulR1 and BulR2 of Streptomyces tsukubaensis: tacrolimus (FK506) and butyrolactone synthetases production control. Appl Microbiol Biotechnol. 98:4919-36. Feb 2014. 24562179
2014 Beites T, Rodríguez-García A, Santos-Beneit F, Moradas-Ferreira P, Aparicio JF & Mendes MV. Genome-wide analysis of the regulation of pimaricin production in Streptomyces natalensis by reactive oxygen species. Appl Microbiol Biotechnol. 98: 2231-2241. Jan 2014. 24413916
2014 Alvarez-Álvarez R, Rodríguez-García A, Santamarta I, Pérez-Redondo R, Prieto-Domínguez A, Martínez-Burgo Y, Liras P. Transcriptomic analysis of Streptomyces clavuligerusΔccaR::tsr: effects of the cephamycin C-clavulanic acid cluster regulator CcaR on global regulation. Microb Biotechnol. 7:221-31. May 2014 24450885
2014 Barreiro C, Martínez-Castro M. Trends in the biosynthesis and production of the immunosuppressant tacrolimus (FK506). Jan 2014 24272367
2014 Hidalgo PI, Ullán RV, Albillos SM, Montero O, Fernández-Bodega MÁ, García-Estrada C, Fernández-Aguado M, Martín JF. Molecular characterization of the PR-toxin gene cluster in Penicillium roqueforti and Penicillium chrysogenum: cross talk of secondary metabolite pathways. Fungal Genet Biol. 62:11-24. Jan 2014. 24239699
2013 Robles-Reglero V, Santamarta I, Álvarez-Álvarez R, Martín JF, Liras P. Transcriptional analysis and proteomics of the holomycin gene cluster in overproducer mutants of Streptomyces clavuligerus.J Biotechnol. Jan 2013 23147422
2013 Fernández-Aguado, M, Teijeira, F, Martín, JF, Ullán, RV, A vacuolar membrane protein affects drastically the biosynthesis of the ACV tripeptide and the beta-lactam pathway of Penicilliumchrysogenum. Appl Microbiol Biotechnol. 97:795-808. Jan 2013. 22777282
2013 Álvarez-Álvarez R, Martínez-Burgo Y, Pérez-Redondo R, Braña AF, Martín JF, Liras P. Expression of the endogenous and heterologous clavulanic acid cluster in Streptomyces flavogriseus: why a silent cluster is sleeping. Applied Microbiology Biotechnology 97:9451-63. Nov 2013. 23974366.
2013 García-Estrada C, Barreiro C, Jami MS, Martín-González J, Martín JF. The inducers 1,3-diaminopropane and spermidine cause the reprogramming of metabolism in Penicillium chrysogenum, leading to multiple vesicles and penicillin overproduction. Jun 2013 23639845
2013 Fernández-Aguado M, Ullán RV, Tejeira F, Rodríguez-Castro R, Martín JF.(2013). A peroxisomal membrane transporter involved in the import of phenylacetic acid for penicillin biosynthesis in Penicillium chrysogenum. Appl Microbiol Biotechnol. 97: 3073-3084. Apr 2013. 23053082
2013 Santos-Beneit F, Rodríguez-García A, Martín JF. Identification of different promoters in the absA1-absA2 two-component system, a negative regulator of antibiotic production in Streptomyces coelicolor. Feb 2013 23247656
2013 Martínez-Castro M, Salehi-Najafabadi Z, Romero F, Pérez-Sanchiz R, Fernández-Chimeno RI, Martín JF, Barreiro C. Taxonomy and chemically semi-defined media for the analysis of the tacrolimus producer Streptomyces tsukubaensis. Appl Microbiol Biotechnol. 2013 97(5):2139-52 22990582
2012 Martín J, García-Estrada C, Kosalková K, Ullán RV, Albillos SM, Martín JF., The inducers 1,3-diaminopropane and spermidine produce a drastic increase in the expression of the penicillin biosynthetic genes for prolonged time, mediated by the laeA regulator.Dec 2012 23089625
2012 Goranovič D, Blažič M, Magdevska V, Horvat J, Kuščer E, Polak T, Santos-Aberturas J, Miriam Martínez-Castro M, Barreiro C, Mrak P, Kopitar G, Kosec G, Fujs S, Martín JF, Hrvoje P. FK506 biosynthesis is regulated by two positive regulatory elements in Streptomyces tsukubaensis. BMC Microbiology 2012 Oct 19;12(1):238. 23083511
2012 Fernández-Aguado, M, Teijeira, F, Martín, JF, Ullán, RV, A vacuolar membrane protein affects drastically the biosynthesis of the ACV tripeptide and the beta-lactam pathway of Penicilliumchrysogenum. Jul 2012. 22777282
2012 Barreiro C, Prieto C, Sola-Landa A, Solera E, Martínez-Castro M, Pérez-Redondo R, García-Estrada C, Aparicio JF, Fernández-Martínez LT, Santos-Aberturas J, Salehi-Najafabadi Z, Rodríguez-García A, Tauch A, Martín JF, Draft Genome of Streptomyces tsukubaensis NRRL 18488, the Producer of the Clinically Important Immunosuppressant Tacrolimus (FK506).J. Bacteriol. 194:3756-7 Jul 2012. 22740677
2012 Santos-Aberturas, J, Vicente, CM, Payero, TD, Martín-Sánchez, L, Cañibano, C, Martín, JF, Aparicio, JF, Hierarchical Control on Polyene Macrolide Biosynthesis: PimR Modulates Pimaricin Production via the PAS-LuxR Transcriptional Activator PimM.PLoS ONE 7:e38536 2012. 22693644
2012 Barreiro C, García Estrada C, Martín JF. Proteomics Methodology Applied to the Analysis of Filamentous Fungi – New Trends for an Impressive Diverse Group of Organisms. 2012. pp: 145-178. En: Applications of Tandem mass Spectrometry. Editor: Prasain J; Co editor: Lay Harn G. Editorial: Intech (Rijeka, Croatia). ISBN 978-953-51-0141-3.
2012 Barreiro, C, Martín, JF, García-Estrada, C, Proteomics shows new faces for the old penicillin producer Penicilliumchrysogenum.J. Biomed. Biotechnol. 2012:105109 2012. 22318718
2012 Domínguez-Santos R., Martín J.F., Kosalková K., Prieto C., Ullán R.V., García-Estrada C. The regulatory factor PcRFX1 controls the expression of the three genes of β-lactam biosynthesis in Penicillium chrysogenum.Fungal Genet Biol. 49:866-881. Nov 2012. 22960281
2012 Martín, JF, Ullán, RV, García-Estrada, C, Role of peroxisomes in the biosynthesis and secretion of β-lactams and other secondary metabolites.J. Ind. Microbiol. Biotechnol. 39:367-82 Mar 2012. 22160272
2012 BARREIRO C., GARCÍA-ESTRADA C., MARTÍN J.F. (2012) Proteomics Methodology Applied to the Analysis of Filamentous Fungi – New Trends for an Impressive Diverse Group of Organisms. In Applications of Tandem mass Spectrometry (Ed. J. Prasain and G. L. Harn). Intech-Open Access Publisher, Rijeka, Croatia., pp. 127-160. ISBN: 978-953-307-870-0.
2012 MARTÍN J.F., GARCÍA-ESTRADA C., ULLÁN R.V. (2012) Genes encoding penicillin and cephalosporin biosynthesis in Acremonium chrysogenum: two separate clusters are required for cephalosporin production. In Biotechnology of fungal genes (ed. V.K. Gupta and M. Ayyachamy). Science Publishers (An Imprint of Edenbridge Ltd, British Channel Islands), Enfield, New Hampshire 03478, USA., pp. 113-138. ISBN: 978-1-57808-787-7.
2012 García-Estrada C. (2012) Bases moleculares de la producción de antibióticos beta-lactámicos. En Aplicación de la Biotecnología en la Ciencia Veterinaria (ed. Fundación Tomás Pascual y Pilar Gómez-Cuétara y Real Academia de Ciencias Veterinarias). IMC-SA, Madrid 28036, Spain. pp. 57-104. ISBN: 978-84-7867-202-8.
2011 García-Estrada, C, Ullán, RV, Albillos, SM, Fernández-Bodega, MÁ, Durek, P, von Döhren, H, Martín, JF, A single cluster of coregulated genes encodes the biosynthesis of the mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum. Chem. Biol. 18:1499-512 Nov 2011. 22118684
2011 Liras P, Santamarta I, Pérez Redondo R. Chapter 9. Clavulanic Acid and Clavams Biosynthesis and Regulation.Streptomyces Molecular Biology and Biotechnology. Norwich(Reino Unido): Editorial: Horizon Scientific Press, 2011. ISBN 978-1-904455-77-6
2011 Santos-Aberturas, J, Payero, TD, Vicente, CM, Guerra, SM, Cañibano, C, Martín, JF, Aparicio, JF, Functional conservation of PAS-LuxR transcriptional regulators in polyene macrolide biosynthesis.Metab. Eng. 13:756-67 Nov 2011. 22001323
2011 Santos-Beneit, F, Barriuso-Iglesias, M, Fernández-Martínez, LT, Martínez-Castro, M, Sola-Landa, A, Rodríguez-García, A, Martín, JF, The RNA polymerase omega factor RpoZ is regulated by PhoP and has an important role in antibiotic biosynthesis and morphological differentiation in Streptomyces coelicolor.Appl. Environ. Microbiol. 77:7586-94 Nov 2011. 21908625
2011 Salehi-Najafabadi Z, Barreiro C, Martínez Castro M, Solera E, Martín JF. Characterization of a gamma-Butyrolactone Receptor of Streptomyces tacrolimicus: Effect on sporulation and tacrolimus biosynthesis. Appl Microbiol Biotechnol. 2011. 92(5): 971-984. 21792593
2011 Salehi-Najafabadi, Z, Barreiro, C, Martínez-Castro, M, Solera, E, Martín, JF, Characterisation of a γ-butyrolactone receptor of Streptomycestacrolimicus: effect on sporulation and tacrolimus biosynthesis.Appl. Microbiol. Biotechnol. 92:971-84 Dec 2011. 21792593
2011 Martín, J, García-Estrada, C, Rumbero, A, Recio, E, Albillos, SM, Ullán, RV, Martín, JF, Characterization of an autoinducer of penicillin biosynthesis in Penicillium chrysogenum. Appl. Environ. Microbiol. 77:5688-96 Aug 2011. 21724894
2011 Teijeira, F, Ullán, RV, Fernández-Aguado, M, Martín, JF, CefR modulates transporters of beta-lactam intermediates preventing the loss of penicillins to the broth and increases cephalosporin production in Acremoniumchrysogenum. Metab. Eng. 13:532-543 Sep 2011. 21704721
2011 Santamarta, I, López-García, MT, Kurt, A, Nárdiz, N, Alvarez-Álvarez, R, Pérez-Redondo, R, Martín, JF, Liras, P, Characterization of DNA-binding sequences for CcaR in the cephamycin-clavulanic acid supercluster of Streptomyces clavuligerus.Mol. Microbiol. 81:968-81 Aug 2011. 21696462
2011 Yepes, A, Rico, S, Rodríguez-García, A, Santamaría, RI, Díaz, M, Novel two-component systems implied in antibiotic production in Streptomyces coelicolor.PLoS ONE 6:e19980 2011. 21625497
2011 Vaca, I, Casqueiro, J, Ullán, RV, Rumbero, A, Chávez, R, Martín, JF, A preparative method for the purification of isopenicillin N from genetically blocked Acremonium chrysogenum strain TD189: studies on the degradation kinetics and storage conditions.J. Antibiot. 64:447-51 Jun 2011. 21522156
2011 Santos-Beneit, F, Rodríguez-García, A, Martín, JF, Complex transcriptional control of the antibiotic regulator afsS in Streptomyces: PhoP and AfsR are overlapping, competitive activators.J. Bacteriol. 193:2242-51 May 2011. 21378195
2011 Nárdiz, N, Santamarta, I, Lorenzana, LM, Martín, JF, Liras, P, A rhodanese-like protein is highly overrepresented in the mutant S. clavuligerus oppA2::aph: effect on holomycin and other secondary metabolites production.Microb Biotechnol 4:216-25 Mar 2011. 21342467
2011 Santos-Aberturas, J, Vicente, CM, Guerra, SM, Payero, TD, Martín, JF, Aparicio, JF, Molecular control of polyene macrolide biosynthesis: direct binding of the regulator PimM to eight promoters of pimaricin genes and identification of binding boxes.J. Biol. Chem. 286:9150-61 Mar 2011. 21187288
2011 García-Rico, RO, Martín, JF, Fierro, F, Heterotrimeric Gα protein Pga1 from Penicillium chrysogenum triggers germination in response to carbon sources and affects negatively resistance to different stress conditions.Fungal Genet. Biol. 48:641-9 Jun 2011. 21146624
2011 Martínez-Castro, M, Barreiro, C, Romero, F, Fernández-Chimeno, RI, Martín, JF, Streptomyces tacrolimicus sp. nov., a low producer of the immunosuppressant tacrolimus (FK506).Int. J. Syst. Evol. Microbiol. 61:1084-8 May 2011. 20525816
2011 Martín, J. F.; Sola-Landa, A.; Santos Beneit, F. & Rodríguez-García, A.Dyson, P., ed., (2011), Streptomyces: Molecular Biology and Biotechnology, Caister Academic Press, chapter Chapter 7 Network mechanisms of phosphate control of primary and secondary metabolism, pp. 137–149.
2011 Liras P., Santamarta I., Pérez-Redondo R. Dyson P., ed., (2011), Streptomyces: Molecular Biology and Biotechnology, Caister Academic Press, Reino Unido. Chapter 9: Clavulanic Acid and Clavams Biosynthesis and Regulation, pp. 167–178.
2011 GARCÍA-ESTRADA C., MARTÍN J.F. (2011) Penicillins and cephalosporins. In Comprehensive Biotechnology (ed. Moo-Young Murray). ELSEVIER, Amsterdam. vol. 3, pp. 255-268. ISBN: 978-0-444-53352-4.
2010 Barreiro C, Jami MS, Garcia-Estrada C, Martín JF. Extracellular and cytoplasmic proteomes of Penicillium chrysogenum reveal the evolution of industrial improvements leading to increased penicillin titers. J Biotechnol. 2010. 150, Supplement 1. 82. S0168165610006036
2010 Barreiro C, Salehi Z, Martínez-Castro M, Martín JF. Gamma-Butyrolactone and Phosphate-Depletion Related Genes Strongly Influence the Sporulation Process of the Immunosuppressant-Producer Strain Streptomyces sp ATCC 55098. J Biotechnol. 2010. 150, Supplement 1. 390-391. S0168165610014057
2010 Martín, JF, Ullán, RV, García-Estrada, C, Regulation and compartmentalization of β-lactam biosynthesis. Microb Biotechnol 3:285-99 May 2010. 21255328
2010 Ullán, RV, Teijeira, F, Guerra, SM, Vaca, I, Martín, JF, Characterization of a novel peroxisome membrane protein essential for conversion of isopenicillin N into cephalosporin C. Biochem. J. 432:227-36 Dec 2010. 20819073
2010 López-García, MT, Santamarta, I, Liras, P, Morphological differentiation and clavulanic acid formation are affected in a Streptomyces clavuligerus adpA-deleted mutant.Microbiology (Reading, Engl.) 156:2354-65 Aug 2010. 20447998
2010 Martín, JF, Liras, P, Engineering of regulatory cascades and networks controlling antibiotic biosynthesis in Streptomyces.Curr. Opin. Microbiol. 13:263-73 Jun 2010. 20303823
2010 Jami, MS, Barreiro, C, García-Estrada, C, Martín, JF, Proteome analysis of the penicillin producer Penicillium chrysogenum: characterization of protein changes during the industrial strain improvement.Mol. Cell Proteomics 9:1182-98 Jun 2010. 20154335
2010 Pérez-Redondo, R, Santamarta, I, Bovenberg, R, Martín, JF, Liras, P, The enigmatic lack of glucose utilization in Streptomyces clavuligerus is due to inefficient expression of the glucose permease gene.Microbiology (Reading, Engl.) 156:1527-37 May 2010. 20110297
2010 GARCÍA-ESTRADA C., FIERRO F., MARTÍN J.F. (2010) Evolution of fungal β-lactam biosynthesis gene clusters. In Microbiology Book Series number 2: Current Research, Technology and Education Topics in Applied Microbiology and Microbial Biotechnology (Volume 1) (ed. A. Méndez-Villas). FORMATEX RESEARCH CENTER, Badajoz, pp.577-588. ISBN (13): 978-84-614-6194-3.
2009 Tunca, S, Barreiro, C, Coque, JJ, Martín, JF, Two overlapping antiparallel genes encoding the iron regulator DmdR1 and the Adm proteins control siderophore [correction of sedephore] and antibiotic biosynthesis in Streptomyces coelicolor A3(2).FEBS J. 276:4814-27 Sep 2009. 19664059
2009 Vicente, CM, Santos-Aberturas, J, Guerra, SM, Payero, TD, Martín, JF, Aparicio, JF, PimT, an amino acid exporter controls polyene production via secretion of the quorum sensing pimaricin-inducer PI-factor in Streptomyces natalensis.Microb. Cell Fact. 8:33 2009. 19505319
2009 García-Estrada, C, Vaca, I, Ullán, RV, van den Berg, MA, Bovenberg, RA, Martín, JF, Molecular characterization of a fungal gene paralogue of the penicillin penDE gene of Penicillium chrysogenum.BMC Microbiol. 9:104 2009. 19470155
2009 Martínez-Castro, M, Solera, E, Martín, JF, Barreiro, C, Efficient pyramidal arrangement of an ordered cosmid library: Rapid screening of genes of the tacrolimus-producer Streptomyces sp. ATCC 55098.J. Microbiol. Methods 78:150-4 Aug 2009. 19445977
2009 Martín, JF, Aparicio, JF, Enzymology of the polyenes pimaricin and candicidin biosynthesis.Meth. Enzymol. 459:215-42 2009. 19362642
2009 Baños, S, Pérez-Redondo, R, Koekman, B, Liras, P, Glycerol utilization gene cluster in Streptomyces clavuligerus.Appl. Environ. Microbiol. 75:2991-5 May 2009. 19286797
2009 Godio, RP, Martín, JF, Modified oxidosqualene cyclases in the formation of bioactive secondary metabolites: biosynthesis of the antitumor clavaric acid.Fungal Genet. Biol. 46:232-42 Mar 2009. 19130892
2009 Kosalková, K, García-Estrada, C, Ullán, RV, Godio, RP, Feltrer, R, Teijeira, F, Mauriz, E, Martín, JF, The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicilliumchrysogenum.Biochimie 91:214-25 Feb 2009. 18952140
2009 Teijeira, F, Ullán, RV, Guerra, SM, García-Estrada, C, Vaca, I, Martín, JF, The transporter CefM involved in translocation of biosynthetic intermediates is essential for cephalosporin production. Biochem. J. 418:113-24 Feb 2009. 18840096
2008 García-Rico, RO, Fierro, F, Mauriz, E, Gómez, A, Fernández-Bodega, MA, Martín, JF, The heterotrimeric Galpha protein pga1 regulates biosynthesis of penicillin, chrysogenin and roquefortine in Penicillium chrysogenum.Microbiology (Reading, Engl.) 154:3567-78 Nov 2008. 18957609
2008 van den Berg, MA, Albang, R, Albermann, K, Badger, JH, Daran, JM, Driessen, AJ, Garcia-Estrada, C, Fedorova, ND, Harris, DM, Heijne, WH, Joardar, V, Kiel, JA, Kovalchuk, A, Martín, JF, Nierman, WC, Nijland, JG, Pronk, JT, Roubos, JA, van der Klei, IJ, van Peij, NN, Veenhuis, M, von Döhren, H, Wagner, C, Wortman, J, Bovenberg, RA, Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.Nat. Biotechnol. 26:1161-8 Oct 2008. 18820685
2008 Ullán, RV, Teijeira, F, Martín, JF, Expression of the Acremonium chrysogenum cefT gene in Penicillum chrysogenum indicates that it encodes an hydrophilic beta-lactam transporter.Curr. Genet. 54:153-61 Sep 2008. 18668246
2008 Ullán, RV, Godio, RP, Teijeira, F, Vaca, I, García-Estrada, C, Feltrer, R, Kosalkova, K, Martín, JF, RNA-silencing in Penicillium chrysogenum and Acremonium chrysogenum: validation studies using beta-lactam genes expression.J. Microbiol. Methods 75:209-18 Oct 2008. 18590779
2008 García-Estrada, C, Ullán, RV, Velasco-Conde, T, Godio, RP, Teijeira, F, Vaca, I, Feltrer, R, Kosalková, K, Mauriz, E, Martín, JF, Post-translational enzyme modification by the phosphopantetheinyl transferase is required for lysine and penicillin biosynthesis but not for roquefortine or fatty acid formation in Penicillium chrysogenum. Biochem. J. 415:317-24 Oct 2008. 18558918
2008 Liras, P, Gómez-Escribano, JP, Santamarta, I, Regulatory mechanisms controlling antibiotic production in Streptomyces clavuligerus.J. Ind. Microbiol. Biotechnol. 35:667-76 Jul 2008. 18446393
2008 García-Estrada, C, Vaca, I, Fierro, F, Sjollema, K, Veenhuis, M, Martín, JF, The unprocessed preprotein form IATC103S of the isopenicillin N acyltransferase is transported inside peroxisomes and regulates its self-processing. Fungal Genet. Biol. 45:1043-52 Jun 2008. 18439860
2008 Gomez-Escribano, JP, Martín, JF, Hesketh, A, Bibb, MJ, Liras, P, Streptomyces clavuligerus relA-null mutants overproduce clavulanic acid and cephamycin C: negative regulation of secondary metabolism by (p)ppGpp.Microbiology (Reading, Engl.) 154:744-55 Mar 2008. 18310021
2007 Godio, RP, Fouces, R, Martín, JF, A squalene epoxidase is involved in biosynthesis of both the antitumor compound clavaric acid and sterols in the basidiomycete H. sublateritium.Chem. Biol. 14:1334-46 Dec 2007. 18096502
2007 Kosalková, K, Rodríguez-Sáiz, M, Barredo, JL, Martín, JF, Binding of the PTA1 transcriptional activator to the divergent promoter region of the first two genes of the penicillin pathway in different Penicillium species.Curr. Genet. 52:229-37 Nov 2007. 17924108
2007 Santamarta, I, López-García, MT, Pérez-Redondo, R, Koekman, B, Martín, JF, Liras, P, Connecting primary and secondary metabolism: AreB, an IclR-like protein, binds the ARE(ccaR) sequence of S. clavuligerus and modulates leucine biosynthesis and cephamycin C and clavulanic acid production.Mol. Microbiol. 66:511-24 Oct 2007. 17877708
2007 Antón, N, Santos-Aberturas, J, Mendes, MV, Guerra, SM, Martín, JF, Aparicio, JF, PimM, a PAS domain positive regulator of pimaricin biosynthesis in Streptomyces natalensis.Microbiology (Reading, Engl.) 153:3174-83 Sep 2007. 17768260
2007 García-Estrada, C, Vaca, I, Lamas-Maceiras, M, Martín, JF.In vivo transport of the intermediates of the penicillin biosynthetic pathway in tailored strains of Penicilliumchrysogenum.Appl. Microbiol. Biotechnol. 76:169-82 Aug 2007. 17516062
2007 Ullán, RV, Campoy, S, Casqueiro, J, Fernández, FJ, Martín, JF, Deacetylcephalosporin C production in Penicillium chrysogenum by expression of the isopenicillin N epimerization, ring expansion, and acetylation genes.Chem. Biol. 14:329-39 Mar 2007. 17379148
2007 Mendes, MV, Recio, E, Antón, N, Guerra, SM, Santos-Aberturas, J, Martín, JF, Aparicio, JF, Cholesterol oxidases act as signaling proteins for the biosynthesis of the polyene macrolide pimaricin.Chem. Biol. 14:279-90 Mar 2007. 17379143
2007 Mendes, MV, Tunca, S, Antón, N, Recio, E, Sola-Landa, A, Aparicio, JF, Martín, JF, The two-component phoR-phoP system of Streptomyces natalensis: Inactivation or deletion of phoP reduces the negative phosphate regulation of pimaricin biosynthesis.Metab. Eng. 9:217-27 Mar 2007. 17142079
2007 GARCÍA-ESTRADA C., MARTÍN J.F. (2007) Penicillin biosynthesis and Secretion: Precursor and Enzyme Localization. In Mycotechnology: Present Status and Future Prospects (ed. Mahendra Rai). I.K. International Publishing House Pvt Ltd, New Delhi, pp.55-83. ISBN 81-89866-08-7.
2006 Recio, E, Aparicio, JF, Rumbero, A, Martín, JF, Glycerol, ethylene glycol and propanediol elicit pimaricin biosynthesis in the PI-factor-defective strain Streptomyces natalensis npi287 and increase polyene production in several wild-type actinomycetes.Microbiology (Reading, Engl.) 152:3147-56 Oct 2006. 17005993
2006 Rodríguez-García, A, Santamarta, I, Pérez-Redondo, R, Martín, JF, Liras, P, Characterization of a two-gene operon epeRA involved in multidrug resistance in Streptomyces clavuligerus.Res. Microbiol. 157:559-68. 2006 Jul-Aug.16797928
2006 Fierro, F, García-Estrada, C, Castillo, NI, Rodríguez, R, Velasco-Conde, T, Martín, JF, Transcriptional and bioinformatic analysis of the 56.8 kb DNA region amplified in tandem repeats containing the penicillin gene cluster in Penicillium chrysogenum.Fungal Genet. Biol. 43:618-29 Sep 2006. 16713314
2006 Liras, P, Martín, JF, Gene clusters for beta-lactam antibiotics and control of their expression: why have clusters evolved, and from where did they originate?Int. Microbiol. 9:9-19 Mar 2006. 16636985
2006 Enríquez, LL, Mendes, MV, Antón, N, Tunca, S, Guerra, SM, Martín, JF, Aparicio, JF, An efficient gene transfer system for the pimaricin producer Streptomyces natalensis.FEMS Microbiol. Lett. 257:312-8 Apr 2006. 16553869
2006 Lamas-Maceiras, M, Vaca, I, Rodríguez, E, Casqueiro, J, Martín, JF, Amplification and disruption of the phenylacetyl-CoA ligase gene of Penicillium chrysogenum encoding an aryl-capping enzyme that supplies phenylacetic acid to the isopenicillin N-acyltransferase.Biochem. J. 395:147-55 Apr 2006. 16321143
2005 Aparicio, JF, Generating novel polyene antifungal drugs.Chem. Biol. 12:509-10 May 2005. 15911369
2005 Santamarta, I, Pérez-Redondo, R, Lorenzana, LM, Martín, JF, Liras, P, Different proteins bind to the butyrolactone receptor protein ARE sequence located upstream of the regulatory ccaR gene of Streptomyces clavuligerus.Mol. Microbiol. 56:824-35 May 2005. 15819635
2005 Mendes, MV, Antón, N, Martín, JF, Aparicio, JF, Characterization of the polyene macrolide P450 epoxidase from Streptomyces natalensis that converts de-epoxypimaricin into pimaricin.Biochem. J. 386:57-62 Feb 2005. 15228385
2004 Martín, JF, Ullán, RV, Casqueiro, J, Novel genes involved in cephalosporin biosynthesis: the three-component isopenicillin N epimerase system. Adv. Biochem. Eng. Biotechnol. 88:91-109 2004. 15719553
2004 Godio, RP, Fouces, R, Gudiña, EJ, Martín, JF, Agrobacterium tumefaciens-mediated transformation of the antitumor clavaric acid-producing basidiomycete Hypholoma sublateritium.Curr. Genet. 46:287-94 Nov 2004. 15480676
2004 de la Fuente, A, Martín, JF, Rodríguez-García, A, Liras, P, Two proteins with ornithine acetyltransferase activity show different functions in Streptomyces clavuligerus: Oat2 modulates clavulanic acid biosynthesis in response to arginine.J. Bacteriol. 186:6501-7 Oct 2004. 15375131
2004 Martín, JF, Phosphate control of the biosynthesis of antibiotics and other secondary metabolites is mediated by the PhoR-PhoP system: an unfinished story.J. Bacteriol. 186:5197-201 Aug 2004. 15292120
2004 Recio, E, Colinas, A, Rumbero, A, Aparicio, JF, Martín, JF, PI factor, a novel type quorum-sensing inducer elicits pimaricin production in Streptomyces natalensis.J. Biol. Chem. 279:41586-93 Oct 2004. 15231842
2004 Aparicio, JF, Mendes, MV, Antón, N, Recio, E, Martín, JF, Polyene macrolide antibiotic biosynthesis.Curr. Med. Chem. 11:1645-56 Jun 2004. 15180569
2004 Lorenzana, LM, Pérez-Redondo, R, Santamarta, I, Martín, JF, Liras, P, Two oligopeptide-permease-encoding genes in the clavulanic acid cluster of Streptomyces clavuligerus are essential for production of the beta-lactamase inhibitor.J. Bacteriol. 186:3431-8 Jun 2004. 15150229
2004 Antón, N, Mendes, MV, Martín, JF, Aparicio, JF, Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis.J. Bacteriol. 186:2567-75 May 2004. 15090496
2004 Naranjo, L, Martín de Valmaseda, E, Casqueiro, J, Ullán, RV, Lamas-Maceiras, M, Bañuelos, O, Martín, JF, Inactivation of the lys7 gene, encoding saccharopine reductase in Penicillium chrysogenum, leads to accumulation of the secondary metabolite precursors piperideine-6-carboxylic acid and pipecolic acid from alpha-aminoadipic acid.Appl. Environ. Microbiol. 70:1031-9 Feb 2004. 14766586
2003 Laich, F, Fierro, F, Martin, JF, Isolation of Penicillium nalgiovense strains impaired in penicillin production by disruption of the pcbAB gene and application as starters on cured meat products.Mycol. Res. 107:717-26 Jun 2003. 12951798
2003 Aparicio, JF, Caffrey, P, Gil, JA, Zotchev, SB, Polyene antibiotic biosynthesis gene clusters.Appl. Microbiol. Biotechnol. 61:179-88 May 2003. 12698274
2002 de la Fuente, A, Lorenzana, LM, Martín, JF, Liras, P, Mutants of Streptomyces clavuligerus with disruptions in different genes for clavulanic acid biosynthesis produce large amounts of holomycin: possible cross-regulation of two unrelated secondary metabolic pathways.J. Bacteriol. 184:6559-65 Dec 2002. 12426344
2002 Ullan, RV, Casqueiro, J, Banuelos, O, Fernandez, FJ, Gutierrez, S, Martin, JF, A novel epimerization system in fungal secondary metabolism involved in the conversion of isopenicillin N into penicillin N in Acremonium chrysogenum.J. Biol. Chem. 277:46216-25 Nov 2002. 12228250
2002 Ullán, RV, Liu, G, Casqueiro, J, Gutiérrez, S, Bañuelos, O, Martín, JF, The cefT gene of Acremonium chrysogenum C10 encodes a putative multidrug efflux pump protein that significantly increases cephalosporin C production.Mol. Genet. Genomics 267:673-83 Jul 2002. 12172807
2002 Santamarta, I, Rodríguez-García, A, Pérez-Redondo, R, Martín, JF, Liras, P, CcaR is an autoregulatory protein that binds to the ccaR and cefD-cmcI promoters of the cephamycin C-clavulanic acid cluster in Streptomyces clavuligerus.J. Bacteriol. 184:3106-13 Jun 2002. 12003953
2002 Mellado, E, Lorenzana, LM, Rodríguez-Sáiz, M, Díez, B, Liras, P, Barredo, JL, The clavulanic acid biosynthetic cluster of Streptomyces clavuligerus: genetic organization of the region upstream of the car gene.Microbiology (Reading, Engl.) 148:1427-38 May 2002. 11988517
2001 Velasco, J, Gutiérrez, S, Casqueiro, J, Fierro, F, Campoy, S, Martín, JF, Cloning and characterization of the gene cahB encoding a cephalosporin C acetylhydrolase from Acremonium chrysogenum.Appl. Microbiol. Biotechnol. 57:350-6 Oct 2001. 11759684
2001 Kosalková, K, Marcos, AT, Martín, JF, A moderate amplification of the mecB gene encoding cystathionine-gamma-lyase stimulates cephalosporin biosynthesis in Acremonium chrysogenum.J. Ind. Microbiol. Biotechnol. 27:252-8 Oct 2001. 11687939
2001 Leitão, AL, Enguita, FJ, Martín, JF, Santos Oliveira, JF, Effect of exogenous lysine the expression of early cephamycin C biosynthetic genes and antibiotic production in Nocardia lactamdurans MA4213.Appl. Microbiol. Biotechnol. 56:670-5 Sep 2001. 11601612
2001 Mendes, MV, Recio, E, Fouces, R, Luiten, R, Martín, JF, Aparicio, JF, Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis.Chem. Biol. 8:635-44 Jul 2001. 11451665
2001 Hernándo-Rico, V, Martín, JF, Santamarta, I, Liras, P, Structure of the ask-asd operon and formation of aspartokinase subunits in the cephamycin producer ‘Amycolatopsis lactamdurans’.Microbiology (Reading, Engl.) 147:1547-55 Jun 2001. 11390685
2001 Gang, L., Casqueiro, J., Gutiérrez, S., Kosalková, K., Castillo, N.I. and J. F. Martín. Elicitation of penicillin biosynthesis by alginate in Penicillium chrysogenum exerted on pcbAB, pcbC and penDE genes at transriptional level. J. Microbiol. Biotechno. 11, 812-818, 2001.
2001 Liu, G, Casqueiro, J, Bañuelos, O, Cardoza, RE, Gutiérrez, S, Martín, JF, Targeted inactivation of the mecB gene, encoding cystathionine-gamma-lyase, shows that the reverse transsulfuration pathway is required for high-level cephalosporin biosynthesis in Acremonium chrysogenum C10 but not for methionine induction of the cephalosporin genes.J. Bacteriol. 183:1765-72 Mar 2001. 11160109
2000 Aparicio, JF, Fouces, R, Mendes, MV, Olivera, N, Martín, JF, A complex multienzyme system encoded by five polyketide synthase genes is involved in the biosynthesis of the 26-membered polyene macrolide pimaricin in Streptomyces natalensis.Chem. Biol. 7:895-905 Nov 2000. 11094342
2000 Liras, P, Rodríguez-García, A, Clavulanic acid, a beta-lactamase inhibitor: biosynthesis and molecular genetics.Appl. Microbiol. Biotechnol. 54:467-75 Oct 2000. 11092620
2000 Chary, VK, de la Fuente, JL, Leitão, AL, Liras, P, Martín, JF, Overexpression of the lat gene in Nocardia lactamdurans from strong heterologous promoters results in very high levels of lysine-6-aminotransferase and up to two-fold increase in cephamycin C production.Appl. Microbiol. Biotechnol. 53:282-8 Mar 2000. 10772467
2000 Mendes, MV, Aparicio, JF, Martín, JF, Complete nucleotide sequence and characterization of pSNA1 from pimaricin-producing Streptomyces natalensis that replicates by a rolling circle mechanism.Plasmid 43:159-65 Mar 2000. 10686136
2000 Kosalková, K, Marcos, AT, Fierro, F, Hernando-Rico, V, Gutiérrez, S, Martín, JF, A novel heptameric sequence (TTAGTAA) is the binding site for a protein required for high level expression of pcbAB, the first gene of the penicillin biosynthesis in Penicillium chrysogenum.J. Biol. Chem. 275:2423-30 Jan 2000. 10644695
1999 Pérez-Redondo, R, Rodríguez-García, A, Martín, JF, Liras, P, Deletion of the pyc gene blocks clavulanic acid biosynthesis except in glycerol-containing medium: evidence for two different genes in formation of the C3 unit.J. Bacteriol. 181:6922-8 Nov 1999. 10559157
1999 Liras, P, Biosynthesis and molecular genetics of cephamycins. Cephamycins produced by actinomycetes.Antonie Van Leeuwenhoek 75:109-24.10422584
1999 Gutiérrez, S, Fierro, F, Casqueiro, J, Martín, JF, Gene organization and plasticity of the beta-lactam genes in different filamentous fungi.Antonie Van Leeuwenhoek 75:81-94. 10422582
1999 Martín, JF, Casqueiro, J, Kosalková, K, Marcos, AT, Gutiérrez, S, Penicillin and cephalosporin biosynthesis: mechanism of carbon catabolite regulation of penicillin production.Antonie Van Leeuwenhoek 75:21-31.10422579
1999 Leitão, AL, Enguita, FJ, De La Fuente, JL, Liras, P, Martin, JF, Inducing effect of diamines on transcription of the cephamycin C genes from the lat and pcbAB promoters in Nocardia lactamdurans.J. Bacteriol. 181:2379-84 Apr 1999. 10197999
1999 Aparicio, JF, Colina, AJ, Ceballos, E, Martín, JF, The biosynthetic gene cluster for the 26-membered ring polyene macrolide pimaricin. A new polyketide synthase organization encoded by two subclusters separated by functionalization genes.J. Biol. Chem. 274:10133-9 Apr 1999. 10187796
1999 Laich, F, Fierro, F, Cardoza, RE, Martin, JF, Organization of the gene cluster for biosynthesis of penicillin in Penicillium nalgiovense and antibiotic production in cured dry sausages.Appl. Environ. Microbiol. 65:1236-40 Mar 1999. 10049889
1999 Casqueiro, J, Gutiérrez, S, Bañuelos, O, Hijarrubia, MJ, Martín, JF, Gene targeting in Penicillium chrysogenum: disruption of the lys2 gene leads to penicillin overproduction.J. Bacteriol. 181:1181-8 Feb 1999. 9973344
1998 Liras, P, Rodríguez-García, A, Martín, JF, Evolution of the clusters of genes for beta-lactam antibiotics: a model for evolutive combinatorial assembly of new beta-lactams.Int. Microbiol. 1:271-8 Dec 1998. 10943374
1998 Enguita, FJ, Coque, JJ, Liras, P, Martin, JF, The nine genes of the Nocardia lactamdurans cephamycin cluster are transcribed into large mRNAs from three promoters, two of them located in a bidirectional promoter region.J. Bacteriol. 180:5489-94 Oct 1998. 9765587
1998 Pérez-Llarena, FJ, Rodríguez-García, A, Enguita, FJ, Martín, JF, Liras, P, The pcd gene encoding piperideine-6-carboxylate dehydrogenase involved in biosynthesis of alpha-aminoadipic acid is located in the cephamycin cluster of Streptomyces clavuligerus.J. Bacteriol. 180:4753-6 Sep 1998. 9721323
1998 Martín, JF, New aspects of genes and enzymes for beta-lactam antibiotic biosynthesis.Appl. Microbiol. Biotechnol. 50:1-15 Jul 1998. 9720195
1998 Pérez-Redondo, R, Rodríguez-García, A, Martín, JF, Liras, P, The claR gene of Streptomyces clavuligerus, encoding a LysR-type regulatory protein controlling clavulanic acid biosynthesis, is linked to the clavulanate-9-aldehyde reductase (car) gene.Gene 211:311-21 May 1998. 9602162
1998 Cubría, JC, Reguera, R, Balaña-Fouce, R, Ordóñez, C, Ordóñez, D, Polyamine-mediated heart hypertrophy induced by clenbuterol in the mouse.J. Pharm. Pharmacol. 50:91-6 Jan 1998. 9580224
1997 Gutiérrez, S, Velasco, J, Marcos, AT, Fernández, FJ, Fierro, F, Barredo, JL, Díez, B, Martín, JF, Expression of the cefG gene is limiting for cephalosporin biosynthesis in Acremonium chrysogenum.Appl. Microbiol. Biotechnol. 48:606-14 Nov 1997. 9421924
1997 de La Fuente, JL, Rumbero, A, Martín, JF, Liras, P, Delta-1-piperideine-6-carboxylate dehydrogenase, a new enzyme that forms alpha-aminoadipate in Streptomyces clavuligerus and other cephamycin C-producing actinomycetes.Biochem. J. 327 ( Pt 1):59-64 Oct 1997. 9355735
1997 Pérez-Llarena, F, Martín, JF, Galleni, M, Coque, JJ, Fuente, JL, Frère, JM, Liras, P, The bla gene of the cephamycin cluster of Streptomyces clavuligerus encodes a class A beta-lactamase of low enzymatic activity.J. Bacteriol. 179:6035-40 Oct 1997. 9324249
1997 Pérez-Llarena, FJ, Liras, P, Rodríguez-García, A, Martín, JF, A regulatory gene (ccaR) required for cephamycin and clavulanic acid production in Streptomyces clavuligerus: amplification results in overproduction of both beta-lactam compounds.J. Bacteriol. 179:2053-9 Mar 1997. 9068654
1996 De la Fuente, JL, Martin, JF, Liras, P, New type of hexameric ornithine carbamoyltransferase with arginase activity in the cephamycin producers Streptomyces clavuligerus and Nocardia lactamdurans.Biochem. J. 320 ( Pt 1):173-9 Nov 1996. 8947483
1996 Kumar, V, de la Fuente, JL, Leitão, AL, Liras, P, Martín, JF, Effect of amplification or targeted disruption of the beta-lactamase gene of Nocardia lactamdurans on cephamycin biosynthesis.Appl. Microbiol. Biotechnol. 45:621-8 Jun 1996. 8766697
1996 Fierro, F, Montenegro, E, Gutiérrez, S, Martín, JF, 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 Jan 1996. 8703430
1996 Enguita, FJ, Liras, P, Leitão, AL, Martín, JF, Interaction of the two proteins of the methoxylation system involved in cephamycin C biosynthesis. Immunoaffinity, protein cross-linking, and fluorescence spectroscopy studies.J. Biol. Chem. 271:33225-30 Dec 1996. 8969179
1995 Rodríguez-García, A, Martín, JF, Liras, P, The argG gene of Streptomyces clavuligerus has low homology to unstable argG from other actinomycetes: effect of amplification on clavulanic acid biosynthesis.Gene 167:9-15 Dec 1995. 8566818
1995 Coque, JJ, Pérez-Llarena, FJ, Enguita, FJ, Fuente, JL, Martín, JF, Liras, P, Characterization of the cmcH genes of Nocardia lactamdurans and Streptomyces clavuligerus encoding a functional 3′-hydroxymethylcephem O-carbamoyltransferase for cephamycin biosynthesis.Gene 162:21-7 Aug 1995. 7557411
1995 Coque, JJ, Enguita, FJ, Martín, JF, Liras, P, A two-protein component 7 alpha-cephem-methoxylase encoded by two genes of the cephamycin C cluster converts cephalosporin C to 7-methoxycephalosporin C.J. Bacteriol. 177:2230-5 Apr 1995. 7721717
1995 Martín, JF, Gutiérrez, S, Genes for beta-lactam antibiotic biosynthesis.Antonie Van Leeuwenhoek 67:181-200 1995. 7771766
1994 Kumar, CV, Coque, JJ, Martín, JF, Efficient Transformation of the Cephamycin C Producer Nocardia lactamdurans and Development of Shuttle and Promoter-Probe Cloning Vectors.Appl. Environ. Microbiol. 60:4086-93 Nov 1994. 16349436
1994 Fernández, FJ, Gutierrez, S, Velasco, J, Montenegro, E, Marcos, AT, Martín, JF, Molecular characterization of three loss-of-function mutations in the isopenicillin N-acyltransferase gene (penDE) of Penicillium chrysogenum.J. Bacteriol. 176:4941-8 Aug 1994. 7519594
1994 Esmahan, C, Alvarez, E, Montenegro, E, Martin, JF, Catabolism of lysine in Penicillium chrysogenum leads to formation of 2-aminoadipic acid, a precursor of penicillin biosynthesis.Appl. Environ. Microbiol. 60:1705-10 Jun 1994. 8031073
1994 Liras, P, Coque, JJ, García-Calzada, J, Pérez Llarena, FJ, Cardoza, RE, [Grouping of the genes of biosynthesis and resistance to beta-lactam antibiotics in cephamycin-C producing actinomycetes].Microbiologia 10:49-56. 7946127
1994 Velasco, J, Gutierrez, S, Fernandez, FJ, Marcos, AT, Arenos, C, Martin, JF, 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. 176:985-91 Feb 1994. 8106341
1993 Fierro, F, Gutiérrez, S, Díez, B, Martín, JF, Resolution of four large 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. 241:573-8 Dec 1993. 8264531
1993 Alvarez, E, Meesschaert, B, Montenegro, E, Gutiérrez, S, Díez, B, Barredo, JL, Martín, JF, The isopenicillin-N acyltransferase of Penicillium chrysogenum has isopenicillin-N amidohydrolase, 6-aminopenicillanic acid acyltransferase and penicillin amidase activities, all of which are encoded by the single penDE gene.Eur. J. Biochem. 215:323-32 Jul 1993. 8344300
1993 Coque, JJ, Liras, P, Martín, JF, Genes for a beta-lactamase, a penicillin-binding protein and a transmembrane protein are clustered with the cephamycin biosynthetic genes in Nocardia lactamdurans.EMBO J. 12:631-9 Feb 1993. 8440253
1993 Cantoral, JM, Gutiérrez, S, Fierro, F, Gil-Espinosa, S, van Liempt, H, Martín, JF, Biochemical characterization and molecular genetics of nine mutants of Penicillium chrysogenum impaired in penicillin biosynthesis.J. Biol. Chem. 268:737-44 Jan 1993. 8416976
1993 Coque, JJ, Martín, JF, Liras, P, Characterization and expression in Streptomyces lividans of cefD and cefE genes from Nocardia lactamdurans: the organization of the cephamycin gene cluster differs from that in Streptomyces clavuligerus.Mol. Gen. Genet. 236:453-8 Jan 1993. 8437592