Tungsten Biocatalysis - Heavy Metal Enzymes for Sustainable Industrial Biocatalysis

欧洲需要一个可持续的化学工业，这只能通过新的突破性技术来实现。工业生物技术建立在化学制造业，提供更有效，更具体，更安全和更少的能源需求的生产，但在工业使用中的酶类数量有限。该项目开辟了一种重要的含钨酶（W-酶）的新酶类，其催化涉及具有挑战性的低氧化还原电位还原反应的惊人化学反应，但目前不可能以经济和规模获得以满足工业需求。我们需要用工业上的主力微生物如大肠杆菌来生产W酶。杆菌然而，我们发现W-辅因子的生物合成是阻碍W-酶在E.杆菌我们可以通过使用我们最近开发的尖端计算酶设计方法来解决这一挑战，为大肠杆菌创建一个全新的W-辅因子生物合成途径。杆菌该项目开发的W-BioCat菌株将能够从基因数据库中表达新的W-酶，并促进新工程W-酶的生产。这些新的W-酶的催化潜力将在新的工艺中建立和实施。令人兴奋的新反应范围在生物催化CO2还原有价值的化学品和桦树减少芳香族化合物将被探索，除了已经建立和广泛适用的羧酸减少。W-BioCat将成为使W-酶可用于工业的突破口。作为一个概念的证明，氢驱动的过程，以转化植物来源的油酸的润肤酯油烯基油酸酯将被创建。油酸油酯用于数百万人日常使用的许多化妆品中。该工艺将在可扩展的工业相关加氢反应器中以多克产量进行演示，并进行市场研究以解决商业化途径。

Europe needs a sustainable chemical industry which will only be realized by new breakthrough technologies. Industrial biotechnology is established in chemical manufacturing, offering more efficient, more specific, safer and less energy demanding production, but is held back by the limited number of enzyme classes in industrial use. This project opens up an important new enzyme class of tungstencontaining enzymes (W-enzymes) which catalyse amazing chemical reactions involving challenging low redox potential reduction reactions, but are currently impossible to obtain economically and on scale to match industrial needs. We need to produce W-enzymes using an industrial workhorse micro-organism such as E. coli. Yet, we discovered that W-cofactor biosynthesisisthe bottleneck preventing successful production of W-enzymes in E. coli. We can solve this challenge by using cutting-edge computational enzyme design approaches we recently developed, to create a completely new W-cofactor biosynthesis pathway for E. coli. The W-BioCat strains developed in this project will enable expression of new W-enzymes from genetic databases, and facilitate production of new engineered W-enzymes. The catalytic potential of these new W-enzymes will be established and implemented in new processes. Exciting new reaction scope in biocatalytic CO2 reduction to valuable chemicals and Birch reduction of aromatic compounds will be explored, alongside the already-established and broadly applicable carboxylic acid reductions. W-BioCat will be the breakthrough to make W-enzymes accessible for industry. As a proof of concept, a hydrogen-driven processto convert plant-derived oleic acid to the emollient ester oleyl oleate will be created. Oleyl oleate is used in many cosmetic products used daily by millions of people. This process will be demonstrated in multi-gram yield in scalable, industrially-relevant hydrogenation reactors, together with market research to address a pathway to commercialisation.