Primary challenges in the upcycling of genetically modified spent microbial biomass.

Precision fermentation is expanding rapidly as a platform for producing high-value proteins and ingredients. This expansion consequently results in a significant increase in genetically modified spent microbial biomass (GMSMB). At present, the dominant industrial practice is to sterilise and dispose of this biomass in landfills. This approach incurs significant costs associated with sterilisation, transport, and waste management, placing financial pressure on producers and limiting the sustainability of the sector. GMSMB is nutrient-rich, often containing high levels of protein, amino acids, vitamins, and other valuable cellular components. This makes it a potentially useful resource for secondary applications. However, the main challenge is to identify economically viable upcycling routes in which the value recovered from GMSMB exceeds or is comparable to the cost of disposal. Several upcycling strategies have been proposed for non-GM spent microbial biomass, particularly from brewing, distilling, and antibiotic production. These include use as animal feed, biofertiliser, biogas substrate, or as a source of value-added biomolecules. Yet, these approaches are not directly transferable to GMSMB, where regulatory restrictions, safety assessments, and public perception present additional barriers. This review examines the key challenges and opportunities associated with GMSMB valorisation. We discuss regulatory frameworks, economic and logistical considerations, consumer acceptance, environmental impacts, and emerging technological strategies for sustainable upcycling. Our aim is to outline the conditions under which GMSMB can transition from a disposal burden to a valuable co-product within the bioeconomy.