Exploring sequence characteristics related to high-level production of secreted proteins in Aspergillus niger

Autor: Johannes Andries Roubos, Liang Wu, Bastiaan A. van den Berg, Marcel J. T. Reinders, Herman Jan Pel, Marc Hulsman, Dick de Ridder
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 10, p e45869 (2012)
PLoS ONE
PLoS ONE, 7 (10), 2012
ISSN: 1932-6203
Popis: Protein sequence features are explored in relation to the production of over-expressed extracellular proteins by fungi. Knowledge on features influencing protein production and secretion could be employed to improve enzyme production levels in industrial bioprocesses via protein engineering. A large set, over 600 homologous and nearly 2,000 heterologous fungal genes, were overexpressed in Aspergillus niger using a standardized expression cassette and scored for high versus no production. Subsequently, sequence-based machine learning techniques were applied for identifying relevant DNA and protein sequence features. The amino-acid composition of the protein sequence was found to be most predictive and interpretation revealed that, for both homologous and heterologous gene expression, the same features are important: tyrosine and asparagine composition was found to have a positive correlation with high-level production, whereas for unsuccessful production, contributions were found for methionine and lysine composition. The predictor is available online at http://bioinformatics.tudelft.nl/hipsec. Subsequent work aims at validating these findings by protein engineering as a method for increasing expression levels per gene copy.
Databáze: OpenAIRE