Novel Gene Targets Discovered for Improving Heterologous Enzyme Production in Aspergillus Niger

Enhance the production of secreted heterologous proteins in fungal host A. niger.

The Science

  • Developed a forward genetics screen coupled with whole-genome resequencing to identify specific lesions responsible for a protein hyper-production phenotype in A. niger.
  • Use bioinformatics to identify loci associated with heterologous enzyme hyper-production.

The Impact

  • Strategy successfully identified novel targets, including a low-affinity glucose transporter, MstC, whose deletion significantly improved secretion of recombinant proteins driven by a glucoamylase promoter. Deletion of mstC loci improved by 4-fold heterologous enzyme production driven by a glucoamylase promoter.
  • Mutations found in the Ypt/Rab GTPase-activating protein of both tested strains might further increase production of heterologous beta-glucosidase if introduced into other heterologous strains.

References

Reilly, M. C., J. Kim, J. Lynn, B. A. Simmons, J. M. Gladden, J. K. Magnuson, and S. E. Baker. 2018. “Forward Genetics Screen Coupled with Whole-Genome Resequencing Identifies Novel Gene Targets for Improving Heterologous Enzyme Production in Aspergillus niger,” Applied Microbiology and Biotechnology 102(4), 1797–807. DOI:10.1007/s00253-017-8717-3.