Engineering Programmable Expression Systems in Aspergillus: Genetic Architecture, Expression Control, Protein Secretion, and Chassis Optimization

Aspergillus species combine eukaryotic protein processing, efficient secretion, and established industrial fermentation, making them important hosts for enzymes, food proteins, and natural products. However, heterologous production is jointly determined by genetic architecture, expression regulation, protein processing and secretion, host physiology, and cultivation conditions rather than by promoter strength alone. This review examines the construction of programmable expression systems in Aspergillus, with emphasis on host selection, DNA maintenance and genome integration, gene dosage and regulatory elements, multigene expression, secretion engineering, and chassis optimization. We further discuss standardized genetic parts and landing sites, quantitative evaluation, high-throughput screening, and product-oriented strain design. Collectively, these advances support a transition from empirical construct-and-screen approaches toward expression systems with more defined genetic structures, tunable outputs, improved production stability, and greater reproducibility and predictability under production-relevant conditions.