An integrated cell and medium engineering approach for production of a nanobody fusion in Saccharomyces cerevisiae.

ABSTRACT: Saccharomyces cerevisiae is an established production host for therapeutic proteins; many of those are small proteins such as insulin or glucagon-like peptide-1 (GLP-1) analogs. Contrastingly, proteins of higher molecular weight, foremost antibodies, did not reach the market due, among other factors, to limiting productivity. Here we addressed the loss of product to protein degradation through a combination of genetic engineering of the host and medium optimization. We screened target genes that either directly or indirectly can lead to proteolytic degradation. We identified four deletions that are beneficial for expression: PEP1 and VPS30, which both can channel proteins to the vacuole for degradation; MON2, which can lead to the re-uptake of secreted proteins; and ALG3, which can affect

SUBMITTER: Niemela LRK 

PROVIDER: S-EPMC12858493 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature