Exploring Sequence Characteristics Related to High- Level Production of Secreted Proteins in Aspergillus niger

Exploring Sequence Characteristics Related to High- Level Production of Secreted Proteins in Aspergillus niger

Van den Berg, B.A.
Reinders, M.J.T.
Hulsman, M.
Wu, L.
Pel, H.J.
Roubos, J.A.
De Ridder, D.

Electrical Engineering, Mathematics and Computer Science

Computer Science & Engineering

2012-10-01

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.

OA-Fund TU Delft

http://resolver.tudelft.nl/uuid:4aafbd92-734b-42c8-bc20-f30e589998de

https://doi.org/10.1371/journal.pone.0045869

Public Library of Science

1932-6203

PLoS ONE, 7 (10), 2012

Institutional Repository

journal article

(c) 2012 The Author(s)
This is an open-access article distributed under the terms of the Creative Commons Attribution License