Gebeyehu Ayele, Habtamu Admassu, Gadissa Mosisa, Abebe Desalegn, Molla Abeje
ABSTRACT The increasing demand for sustainable protein sources has accelerated the exploration of alternative systems that reduce environmental impact while maintaining nutritional value. Single‐cell protein (SCP) produced from microorganisms including bacteria, yeasts, fungi, and microalgae offers a resource‐efficient solution. Fruit processing residues (peels, pomace, and pulp) represent abundant, carbohydrate‐rich substrates suitable for microbial conversion, supporting waste valorization within a circular bio‐economy. Microbial protein content typically ranges from 30% to 55% (dry weight) under standard cultivation conditions; however, values approaching ~80% have been reported in optimized systems, particularly with selected strains and controlled fermentation environments. This variability is governed by multiple interacting factors, including substrate composition and pretreatment, carbon‐to‐nitrogen (C/N) ratio, pH, temperature, aeration, inoculum density, fermentation time, oxygen transfer, and metabolic characteristics of the microorganism. Given these interactions, Response Surface Methodology (RSM), including Box–Behnken and Central Composite designs, provides a statistically robust approach for modeling process variables and identifying optimal conditions with reduced experimental effort. Compared to one‐factor approaches, RSM enables more reliable detection of interaction effects and operational optima, although improvements are system‐dependent. Despite progress at laboratory scale, challenges remain in process scale‐up, reproducibility, energy efficiency, and techno‐economic feasibility, alongside limited integration of life‐cycle and regulatory considerations. Future work should combine statistically optimized fermentation with pilot‐scale validation and standardized reporting to support scalable and sustainable SCP production from fruit‐derived substrates.