Gebeyehu Ayele, Habtamu Admassu, Gadissa Mosisa, Abebe Desalegn, Molla Abeje
Single-cell protein (SCP) has gained attention as a sustainable alternative to traditional food and feed proteins, driven by the increasing global demand for high-quality protein. Although SCP production from agricultural wastes is not a new topic, it remains highly relevant due to the abundance and low cost of ligno-cellulosic and starchy residues, which serve as substrates for microbial growth. Direct microbial utilization of these wastes is limited by structural complexity, necessitating pretreatment to enhance sugar availability, reduce inhibitors, and improve protein yield. Traditional physical, chemical, and biological pretreatments have limitations such as high energy demand, cost, or environmental impact. Emerging technologies including ultrasound, microwave-assisted hydrolysis, supercritical fluids, ionic liquids, deep eutectic solvents, hydrothermal processes, and plasma/ozone treatments have shown improved efficiency, reduced inhibitor formation, and better substrate digestibility specifically for SCP production. This review critically summarizes these advances, compares their effects on fermentable sugar release, microbial growth, and protein yields, and highlights hybrid and green pretreatment strategies as the most promising for scalable applications. Quantitative insights and literature analysis reveal that SCP biomass and protein content can be significantly enhanced through optimized pretreatment and downstream microbial fermentation. Future directions emphasize regulatory frameworks, process intensification, cost-effective scale-up, and environmental assessment to support industrial adoption. Converting agricultural residues into high-value SCP using these novel pretreatment technologies offers a sustainable route to enhance global food security and promote a circular bio-economy.