[14-ERA IB] MetaCat: A metagenomic collection of novel and highly efficient biocatalysts for industrial biotechnology

化学和生物工业对酶生物催化剂的需求稳步增长，酶生物催化剂可以催化各种不同的化学反应，具有高活性、底物特异性和对映体选择性。然而，酶已经进化为在活细胞和温和的反应条件下工作；因此，大多数酶不能直接应用于工业过程。虽然已知很少有适合生物技术应用的酶存在，但其分子基础尚不清楚。MetaCat项目将提供创新的工具和知识，用于识别这种强大的“全方位频繁撞击”酶（AFHs）。宏基因组资源将通过新的基于功能和序列的筛选来鉴定腈酶、转氨酶、酮还原酶、糖基水解酶和脂肪酶/酯酶。宏基因组学和元催化的结合将与基于结构和高通量的技术、模拟具有挑战性的化学合成步骤的通用模型底物、下一代测序技术以及硅数据挖掘技术一起使用。利用合成生物学方法开发新的遗传工具，构建基于无细胞功能的筛选平台，以更快、更好地进行筛选。将建立一种创新的单细胞激光捕获技术，以获得新的以前未知的酶多样性。鉴定的酶将形成一个可销售的多功能生物催化剂集合，以及一个全面的数据库，可以用作建模和体外进化实验的起点。它们将用于改善化学品生产过程，例如时间表，产品纯度，环境可持续性，并将导致增值产品。因此，MetaCat将有助于缩短生物技术过程的发展时间表，从而使工业生物催化更具吸引力和利润。

Chemical and bio-industries have a steadily growing demand for enzyme biocatalysts, which can catalyze a huge variety of different chemical reactions with high activity, substrate specificity and enantioselectivity. However, enzymes have been evolved by nature to work in living cells and under mild reaction conditions; consequently, most enzymes cannot be applied in industrial processes directly. Although it is known that few enzymes exist, which are well suited for biotechnological applications, the molecular basis is unknown. The MetaCat project will deliver innovative toolsand knowledge for the identification of such robust "all-round frequent hit" enzymes (AFHs).Metagenomic resources will be exploited by novel function- and sequence-based screenings to identify nitrilases, transaminases, ketoreductases, glycosyl hydrolases and lipases/esterases. A combination of metagenomics and metacatalysis will be used together with structure-based andhigh-throughput technologies, generic model substrates mimicking challenging chemical synthesis steps, next generation sequencing technologies as well as in silico data mining. New genetic tools using synthetic biology approaches will be developed to construct a cell-free function-basedscreening platform for faster and improved screening. An innovative single-cell laser trapping technology will be established to give access to a new previously unknown enzyme diversity. The identified enzymes will form a marketable versatile biocatalyst collection together with a comprehensive database and can be used as starting points for modeling and in vitro evolution experiments. They will be applied to improve chemical production processes regarding e.g. timelines, purity of the products, environmental sustainability and will lead to value-added products.Thus, MetaCat will contribute to shorten timelines for development of biotechnological processes and thus to make industrial biocatalysis more attractive and profitable.