Bioengineering microbial cellulose synthesis pathways as biofactory for industrial-scale cellulose production: a...

Microbial cellulose (MC) is a natural biopolymer distinguished by its chemical purity, nanofibrillar architecture, eco-friendliness, biodegradability, and mechanical properties. These distinctive features of MC have expanded the potential applications across diverse fields. However, its transition from laboratory-scale production to industrial manufacturing remains constrained by its low productivity, high production costs, genetic instability of the cellulose-producing strains, accumulation of inhibitory by-products, and inadequate oxygen supply during the fermentation process. These limitations are further complicated by poor standardization of the relationship between the engineered biosynthetic pathways and the resulting physicochemical properties of cellulose. Hence, this review critically examines MC biosynthesis pathways across bacteria, algae, and oomycetes, with particular emphasis on the bacteria as the most advanced biofactory for MC production. Recent advances in metabolic engineering, genome editing, and synthetic biology have opened unprecedented avenues to enhance large-scale cellulose productivity by optimizing precursor pathways, suppressing byproduct formation, engineering cyclic-di-GMP regulatory networks, efficient oxygen utilization, and developing synthetic biology toolkits. Finally, we identify key research priorities including development of genetically stable microbial strains, improved oxygen-management strategies, and integrated strain-process engineering required to translate MC production from laboratory to commercially viable biofactories. In parallel, innovations in technology like advanced fermentation strategy and bioreactor designs are the crucial determinants for accelerating MC production, bridging the gaps between experimental conditions and commercial implementation. Altogether, these advancements will lay the foundation and pave the way for developing efficient cellulose biofactories to meet the increasing demand for high-quality and sustainable biomaterials, fostering the transition towards a resource-efficient, eco-friendly future.