Recent advances in the development of Aspergillus for protein production.

Aspergillus had been widely used in the industrial production of recombinant proteins. In addition to the safety and broad substrate utilization spectrum, its efficient post-translational modification and strong protein secretion capacity have significant advantages for developing an excellent protein-producing cell factory in industrial production. However, the difficulties in genetic manipulation of Aspergillus and varying expression levels of different heterologous proteins hampered its further development and application. Recently, the development of CRISPR genome editing and high-throughput screening platforms has facilitated the Aspergillus development of a wide range of modifications and applications. Meanwhile, multi-omics analysis and multiplexed genetic engineering have promoted effective knowledge mining. This paper provides a comprehensive and updated review of these advances, including high-throughput screening, genome editing, protein expression modules, and fermentation optimization. It also highlights and discusses the latest significant progress, aiming to provide a practical guide for implementing Aspergillus as an efficient protein-producing cell factory.