The major bottleneck for plant biomass processing is fiber saccharification: the conversion of cell wall lignocellulosic biomass into fermentable sugars (en route to production of value-added chemicals like second generation biofuels). Some microbes enhance this step by using natural self-assembling proteinaceous nanocatalists known as cellulosomes. CellulosomePlus targets rational design of optimized cellulosomes to overcome this problem.This would allow efficient production of biofuels from low-value raw materials like inedible parts of plants and industrial residues (which are all renewable, sustainable and inexpensive). First we propose to characterize the physicochemical and structural properties (including mechanostability) as well as interactions of enzymes and scaffolds from natural cellulosomes and non-cellulosomal components. In parallel, we will characterize a suitable residual substrate from municipal waste (organic fraction of municipal solid waste) and develop improved assays to reliably follow cellulosomal enzymatic activity. The acquired knowledge will be complemented with rapid computational modelling at the atomic and supramolecular levels for testing and predictions. Experimental and theoretical knowledge will be then integrated to design improved cellulosomes (with high-selectivity, activity and cost-effectiveness). Further improvement will be obtained by iteration using high throughput screening of components. The improved cellulosomes generated through this innovative multidisciplinary approach represent a step towards green chemistry since they are biodegradable proteinaceous materials and therefore by-products and/or wastes are minimized due to the high enzymatic selectivity. Finally, the production of the optimized cellulosomes (and the process involved) will be scaled up to preindustrial scale to demonstrate their viable commercial production. These results will be patented and a roadmap will be drawn up towards future standardization.