(62a) Setting Biorefinery Manufacturing Fundamentals to Produce a Portfolio of Commodity and Fine Chemicals

 The chemurgy concept, that is, manufacturing industrial commodity and chemical products from organic raw materials such as agricultural biomass and lignocellulosic waste, predates the petrochemical industry. However, petrochemicals prevailed over fermentation chemicals given critical industrialization factors, comprising a low cost of the petroleum feedstock and a high process economic efficiency, as exemplified by the full utilization of products and by-products from petrochemical plants for the production of gasoline. These economies of scale and scope have played an important role in the booming industrial development at the beginning of the XX^th century and were realized on a very large scale in World War II and the following decades¹.

 These extremely efficient cost structures that have been derived in the petrochemical industry over a century are now both a blessing and a curse. The blessing is that these economies of scale and scope have made possible the manufacturing of cheap fuels and materials. The resulting abundant supply of chemicals for industry and transportation has enabled modern life and thus now appear to be indispensable. The curse is that efforts to displace and replace the petroleum industry by the chemurgy industry for alleviating global warming and fossil fuel supply threats meet a very high economic and resistance barrier². This has resulted over the years in a detrimental delay in renewable chemistry technology investment, development, and deployment³.

 The biorefinery concept aims at recreating for agricultural feedstock cost structures that are similarly enabling as the ones at play in the petrochemical industry^{4, 5}. This change is of course fundamental and will have far reaching consequences, as it integrates the agricultural value chain into the petrochemical value chain, thus colliding the transportation, polymer, and chemical value chains with other established value chains and notably of the food and feed industry³. A key difference nevertheless remains in that the higher oxygen content of biomass-based compounds makes possible to produce totally novel materials and chemicals with novels properties⁶. An enabling factor of the biorefinery vision is of course the availability of versatile, cost-effective, and robust industrial processes to manufacture an array of chemicals to serve various sectors including the fuel, chemical, industrial polymer, feed, food, cosmetic, and pharmaceutical industries. Notably, it is important for the biorefinery plant manager to be able to produce in addition to fuels, such as ethanol or isobutanol, higher value compounds for the chemical industry, such as ethyl-acetate or isobutanol.

 We report here on a growth-arrested biotechnological process to manufacture ethanol, organic acids, and amino acids from mixed sugars, based on Corynebacterium glutamicum, an organism that has a long history of use to produce amino acids as feed and food supplements or cosmetic ingredients. The intrinsic design of the process is to decouple in a separate fermentor and a reactor biological catalyst-production and product-production phases⁷ with cell recycling and using very high cell concentrations; it builds upon the intrinsic properties of this organism. C. glutamicum is a facultative anaerobic bacterium that grows in the absence of oxygen only in media containing a terminal electron acceptor such as nitrate⁸. C. glutamicum does not sporulate but remains metabolically active when placed under growth-arrested conditions^{9, 10} and is not inhibited by common fermentation inhibitors present in typical lignocellulosic hydrolysates^{11, 12}; moreover, it can catabolize a range of sugars in parallel with glucose^{7, 13, 14}. A complete toolbox of molecular tools enables one to modulate at will its plastic genome and general metabolism^{10, 15}. The RITE process presents the entire set of fundamental attributes necessary for reaching cost-effectiveness and enabling a rich product portfolio: simplicity, industrial robustness¹⁶, raw material versatility (glucose, fructose, glucuronic acid, glucosamine, maltose, mannose, α-methyl-glucoside, ribose, sucrose, trehalose, arbutin, salicin, cellobiose, arabinose, xylose)^{13, 14, 17, 18}, product versatility (ethanol, organic acids, amino acids)^{9, 16, 19, 20}, reduced utilities requirement (reduced fermentation heat¹², no oxygenation requirement⁹), high conversion rates of carbohydrate feedstocks-to-product given cell recycling and the absence of growth requirements (e.g., 110 gl^-1 or 40 gl^-1h^-1 D-lactate)²¹, possibility to conduct continuous fermentations for long periods of time, dramatically reduced risks of contamination in the reaction vessel given the use of very high cellular concentrations, secreted product, no expensive reagent, portfolio of processes that enable the practitioner to manage the biorefinery plant in swiftly interchangeable processes or to capture synergies by implementing multiplex productions²².

 The stage is now set for this core technology to be translated into a biorefinery demonstration plant, as a first step towards full-scale commercialization.

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