Tuning biaryl-bridged antibacterial peptides via biotransformation with tyrosinase enzymes

Professor Alethea B Tabor (ABT) (primary)
Professor John M Ward (JMW) (secondary)
Biochemical Engineering


Biaryl bridged macrocyclic peptides, such as vancomycin, are key privileged structures for the development of new antibacterials. Synthetic routes to these structures are usually long and use hazardous or toxic reagents. There is therefore a pressing need to develop greener biotransformation routes from simpler structures, or via functionalisation of natural products, to give rapid access to panels of analogues that can be screened for antibacterial activity. In this project we will develop chemoenzymatic routes to analogues of the arylomycins, using wild-type and mutant tyrosinase enzymes in the key biotransformation step, and will screen these against Gram -ve ESKAPE pathogens.


[1] P. A. Smith et al., Optimised arylomycins are a new class of Gram-negative antibiotics. Nature, 561, 189 (2018)
[2] Y. Wang, N. Tappertzhofen, D. Mendez-Sanchez, M. Bawn, B. Lyu, J. M. Ward, H. C. Hailes, Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids. Angew. Chem. Int. Ed. Engl., 58, 10120 (2019)
[3] D. S. Peters, F. E. Romesberg, P. S. Baran, Scalable Access to Arylomycins via C–H Functionalization Logic. J. Am. Chem. Soc., 140, 2072 (2018)
[4] B. R. Lichman, J. Zhao, H. C. Hailes, J. M. Ward, Enzyme catalyzed Pictet-Spengler formation of chiral 1,1’-disubstituted- and spiro-tetrahydroisoquinolines. Nature Commun., 8, 14883 (2017)
[5] M. Paetzel, Structure and mechanism of Escherichia coli type I signal peptidase. Biochim. Biophys. Acta. 1834, 1497 (2014)

Molecules, cells and industrial biotechnology
Area of Biology
Chemical BiologyMicrobiology
Techniques & Approaches
ChemistryMolecular Biology