Coupling CAR to UbiD: in vivo functionalization of aromatic compounds
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
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.
Organisations
People |
ORCID iD |
David Leys (Primary Supervisor) | http://orcid.org/0000-0003-4845-8443 |
Publications
Aleku GA
(2020)
Enzymatic C-H activation of aromatic compounds through CO2 fixation.
in Nature chemical biology
Aleku GA
(2021)
Synthetic Enzyme-Catalyzed CO2 Fixation Reactions.
in ChemSusChem
Bloor S
(2022)
Prenylated flavins: structures and mechanisms
in The FEBS Journal
Marshall SA
(2021)
UbiD domain dynamics underpins aromatic decarboxylation.
in Nature communications