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

The Science

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

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.

Summary

• 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.

References

Reilly, M.C. et al. “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), 1797–1807 (2018). [DOI:10.1007/s00253-017-8717-3]