Multidimensional strategies for efficient heterologous protein expression in Aspergillus niger

Microbial protein is a promising alternative to animal and plant proteins. Aspergillus niger, a generally recognized as safe (GRAS) microorganism, is frequently used for heterologous protein production, although its expression efficiency is constrained by multiple factors, including gene transcription, metabolic flux distribution, protein folding, and secretion pathways. However, constructing universal Aspergillus niger chassis cells for efficient protein production remains challenging due to the diverse properties of different proteins. With advancements in synthetic biology, numerous molecular biology tools and metabolic engineering strategies have been employed to address these issues. This article summarizes and discusses the latest progress in enhancing heterologous protein production from five dimensions: expression systems, secretion pathways, metabolic flux, intelligent fermentation, and systematic optimization through multi-omics integration. Additionally, it prospects the efficient and sustainable production of heterologous proteins by Aspergillus niger.