Unwrapping the genome of a protein µfactory

August 25th, 2009 by Francis Martin Leave a reply »

PicpaThe methylotrophic yeast Pichia pastoris has become a highly successful system for the expression of heterologous genes. It is widely used for the production of recombinant proteins. Several factors have contributed to its rapid acceptance, the most important of which include (1) A promoter derived from the alcohol oxidase I (AOX1) gene of P. pastoris that is uniquely suited for the controlled expression of foreign genes, (2) The strong preference of P. pastoris for respiratory growth, a physiological feature that greatly facilitates its culturing at high cell densities relative to fermentative yeasts and (3) strains capable of human-type N-glycosylation are available increasing the utility of this ‘humanized’ yeast for biopharmaceutical production. In addition, P. pastoris is a widely used model organism for studying peroxisomal biogenesis and methanol assimilation.

In the June issue of Nature Biotechnology, Nico Callewaert’s group (from Ghent VIB) published the genome sequence of P. pastoris. To my knowledge, this  is the first fungal genome published that has been assembled exclusively from ‘454 GS-FLX’ reads. Using this approach, they highly oversampled the genome (897,000, 20 times coverage) and generated 70,500 paired-end sequence tags, to enable the assembly of all but seven contigs into nine ‘supercontigs’ (plus the mitochondrial genome). The genome is organized in four chromosomes with a total estimated size of 9.4 Mbp and 5,313 protein-coding genes. To facilitate the ‘customization’ of novel strains for protein production, in-depth gene curations of genes involved in protein secretion, protein glycosylation and protein degradation were performed. The wealth of information generated by these genome sequence and annotation will likely facilitate the design of highly productive biopharmaceutical strains.

De Schutter, K., Lin, Y.-C., Tiels, P., Van Hecke, A., Glinka, S., Weber-Lehmann, J., Rouzé, P., Van de Peer, Y., Callewaert, L. (2009) Genome sequence of the recombinant protein production host Pichia pastoris, a methylotrophic yeast. Nature Biotechnology 27, 561 – 566.

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