Manipulation of genes involved in signal transduction to control fungal morphology during fermentation and production
AssigneeZymergen Inc.
InventorsKenneth S. Bruno, Sachin Jain, Brandon Pfannenstiel, Edyta Szewczyk
Life of this patent
Estimating the term…
Abstract
The present disclosure provides a microbial genomic engineering method and system for transforming, screening, and selecting filamentous fungal cells that have altered morphology and/or growth under specific growth conditions. The method and system utilize high-throughput (HTP) methods to produce filamentous fungal production strains with a desired morphological phenotype.
Claims16
A variant strain of Aspergillus that is genetically altered compared to a parental strain, wherein cells of the variant strain possess a genetic alteration in an osmotic response pathway gene that causes cells of the variant strain to produce a reduced amount and/or less active form of functional protein encoded by the osmotic response pathway gene as compared to cells of the parental strain when grown under submerged culture conditions,
- wherein the osmotic response pathway gene is selected from an Aspergillus niger (A. niger) orthologue of a Saccharomyces cerevisiae (S. cerevisiae) sln1 gene and a Neurospora crassa (N. crassa) nik1 gene, and wherein the genetic alteration is replacement of a native promoter of the osmotic response pathway gene with a promoter that weakly expresses the osmotic response pathway gene compared to the native promoter, wherein the promoter that weakly expresses the osmotic response pathway gene as compared to the native promoter is selected from an Aspergillus amyB gene promoter and an Aspergillus manB gene promoter.
A variant strain of Aspergillus that is genetically altered compared to a parental strain, wherein cells of the variant strain possess an osmotic response pathway gene comprising a nucleic acid sequence selected from SEQ ID NO:
- 14 and SEQ ID NO:
- 76 operably linked to a manB gene promoter comprising the nucleic acid sequence of SEQ ID NO:
- 1 that causes cells of the variant strain to produce a reduced amount and/or less active form of functional protein encoded by the osmotic response pathway gene comprising the nucleic acid sequence of SEQ ID NO:
- 14 or SEQ ID NO:
- 76 as compared to cells of the parental strain when grown under submerged culture conditions.
Dependencies are inferred from the claim text.