Coupling CAR to UbiD: in vivo functionalization of aromatic compounds

容易获得的芳香族化合物，如苯或萘的官能化需要苛刻的条件。在其他修饰中，自然通过UbiD酶的作用利用这些化合物的可逆羧化作用(1)。我们最近展示了UbiD酶如何与UbiX协同完成这一非凡的反应(2，3)。此外，我们最近确定了第一个CAR酶的结构，这是一种具有广泛底物专一性的羧酸还原酶(4)。这两种酶的结合(即UbiD/X和CAR)应该允许芳香族化合物在体内通过羧酸中间体转化为高价值的产物，如醛或酰胺。为此，我们试图研究一系列UbiD/X和CAR酶，以探索利用这些蛋白质的组合来实现芳香族功能化的范围。研究将在MIB(www.mib.ac.uk)进行，为蛋白质生物化学、酶特性、结构生物学和合成生物学提供最先进的基础设施。除了分析化学、有机化学和建模外，您还将能够接触到各种学科，重点是酶特性(包括结构生物学/蛋白质结晶学)和进化，并在David Leys、Nick Turner和Neil Dixon小组中提供多学科培训。该项目将适合对未来的酶学/结构生物学、生物技术、生物催化和生物加工领域的职业感兴趣的个人。

Functionalization of readily available aromatic compounds such as benzene or naphthalene requires harsh conditions. Among other modifications, Nature makes use of reversible carboxylation of these compounds through action of the UbiD enzyme (1). We have recently demonstrated how the UbiD enzyme in concert with UbiX achieves this remarkable reaction (2,3). In addition, we have recently determined the structure of the first CAR enzyme, a carboxylic acid reductase with broad substrate specificity (4). Combination of both enzyme activities (ie UbiD/X and CAR) should allow for convertion of aromatic compounds into high value products such as aldehydes or amides via the carboxylic acid intermediate in vivo. To this end, we seek to study a range of UbiD/X and CAR enzymes, to explore the scope for aromatic functionalization using combinatorial combination of these proteins. Research will be carried out at the MIB (www.mib.ac.uk), providing state-of-the art infrastructure for protein biochemistry, enzyme characterization, structural biology and synthetic biology. You will be able to engage with various disciplines, with an emphasis on enzyme characterization (including structural biology/protein crystallography) and evolution, in addition to analytical chemistry, organic chemistry and modeling, providing a multidisciplinary training in the groups of David Leys, Nick Turner and Neil Dixon. This project would suit individuals interested in future careers in enzymology/structural biology, biotechnology, biocatalysis and bioprocessing.