Understanding and exploiting microbial machines towards antibiotic discovery

Sarah Barry (primary)
King's College London
James Mason (secondary)
Institute of Pharmaceutical Sciences
King's College London


Bacteria are the largest source of clinically used antibiotics. Genome sequencing of bacterial strains has identified hundreds of pathways responsible for antibiotic production. As antibiotic resistance is now a global problem (http://www.who.int/antimicrobial-resistance/en/) many scientists are interested in using synthetic biology to engineer bacteria to produce new antibiotics. We are currently studying a biochemical pathway in a bacterial strain responsible for producing a cyclic peptide antibiotic with activity against tuberculosis. The goal of this project is to elucidate this pathway using mutagenesis, characterize key biosynthetic enzymes and engineer the enzymes to produce new derivatives.


1) Ma, J et al., Nat Commun, 2017, 8: 391
2) Alkhalaf, L. M., Barry, S. M., Rea, D., Gallo, A., Griffiths, D., Lewandowski, J., Fulop, V., Challis, G. L. Binding of Distinct Substrate Conformations Enables Hydroxylation of Remote Sites in Thaxtomin D by Cytochrome P450 TxtC J. Am. Chem. Soc. 2018, DOI: 10.1021/jacs.8b08864
3) Hubert, C. B. and Barry, S. M. New Chemistry from Natural Product Biosynthesis Biochem. Soc. Trans. 2016, 44, 738-744
4)Man, D.W-W., Kanno, T., Manzo, G., Robertson, B.D., Lam, J.K.W. & Mason, A.J. Rifampin or capreomycin induced remodelling of the Mycobacterium smegmatis mycolic acid layer is mitigated in synergistic combinations with cationic antimicrobial peptides. mSphere 2018 3: e00218-18
5)Zhao, Q, et al Recent advances in natural products exploitation in Streptomyces via synthetic biology (2019) https://doi.org/10.1002/elsc.201800137

Molecules, cells and industrial biotechnology
Area of Biology
BiotechnologyChemical Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsChemistryMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology