Expression of a synthetic copy of the bovine chymosin gene in Aspergillus awamori from constitutive and pH-regulated promoters and secretion using two different pre-pro sequences.

[EN] A copy of the bovine chymosin gene (chy) witha codon usage optimized for its expression in Aspergillusawamori was constructed starting from synthetic oligo-nucleotides. To study the ability of this filamentous fun-gus to secrete bovine prochymosin, two plasmids wereconstructed in which the tran...

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Detalles Bibliográficos
Autores: Cardoza, Rosa E., Gutiérrez , Santiago 1965-, Ortega, Néstor, Colina, Ángel, Casqueiro Blanco, Francisco Javier, Martín Martín, Juan Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2003
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/21809
Acceso en línea:http://hdl.handle.net/10612/21809
https://doi.org/10.1002/bit.10666
Access Level:acceso abierto
Palabra clave:Biotecnología
Filamentous fungi
Synthetic chymosin gene
Heterologous protein overexpression
pH-regulated promoters
2414 Microbiología
2414.06 Hongos
2415.01 Biología Molecular de Microorganismos
3302.03 Microbiología Industrial
Descripción
Sumario:[EN] A copy of the bovine chymosin gene (chy) witha codon usage optimized for its expression in Aspergillusawamori was constructed starting from synthetic oligo-nucleotides. To study the ability of this filamentous fun-gus to secrete bovine prochymosin, two plasmids wereconstructed in which the transcriptional, translational,and secretory control regions of the A. nidulans gpdAgene and pepB genes were coupled to either preprochy-mosin or prochymosin genes. Secretion of a protein en-zymatically and immunologically indistinguishable frombovine chymosin was achieved in A. awamori transfor-mants with each of these constructions. In all cases,the primary translation product (40.5 kDa) was self-processed to a mature chymosin polypeptide having amolecular weight of 35.6 kDa. Immunological assays in-dicated that most of the chymosin was secreted to theextracellular medium. Hybridization analysis of genomicDNA from chymosin transformants showed chromosom-al integration of prochymosin sequences and, in sometransformants, multiple copies of the expression cas-settes were observed. Expression from the gpdA pro-moter was constitutive, whereas expression from thepepB promoter was strongly influenced by pH. A veryhigh expression from the pepB promoter was observedduring the growth phase. The A. awamori pepB geneterminator was more favorable for chymosin productionthan the S. cerevisiae CYC1 terminator.