Imperial College London
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Professor Jake Baum

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 5420jake.baum Website

 
 
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Location

 

c/o Baum labSir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Wilkinson:2019:10.1101/814715,
author = {Wilkinson, M and Lai, H-E and Freemont, P and Baum, J},
doi = {10.1101/814715},
publisher = {bioRxiv},
title = {A biosynthetic platform for antimalarial drug discovery},
url = {http://dx.doi.org/10.1101/814715},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - ABSTRACT Advances in synthetic biology have enabled production of a variety of compounds using bacteria as a vehicle for complex compound biosynthesis. Violacein, a naturally occurring indole pigment with antibiotic properties, can be biosynthetically engineered in Escherichia coli expressing its non-native synthesis pathway. To explore whether this synthetic biosynthesis platform could be used for drug discovery, here we have screened bacterially-derived violacein against the main causative agent of human malaria, Plasmodium falciparum . We show the antiparasitic activity of bacterially-derived violacein against the P. falciparum 3D7 laboratory reference strain as well as drug-sensitive and resistant patient isolates, confirming the potential utility of this drug as an antimalarial. We then screen a biosynthetic series of violacein derivatives against P. falciparum growth. The demonstrated varied activity of each derivative against asexual parasite growth points to potential for further development of violacein as an antimalarial. Towards defining its mode of action, we show that biosynthetic violacein affects the parasite actin cytoskeleton, resulting in an accumulation of actin signal that is independent of actin polymerization. This activity points to a target that modulates actin behaviour in the cell either in terms of its regulation or its folding. More broadly, our data show that bacterial synthetic biosynthesis is a suitable platform for antimalarial drug discovery with potential applications in high-throughput and cost-effective drug screening with otherwise chemically-intractable natural products.
AU  - Wilkinson,M
AU  - Lai,H-E
AU  - Freemont,P
AU  - Baum,J
DO  - 10.1101/814715
PB  - bioRxiv
PY  - 2019///
TI  - A biosynthetic platform for antimalarial drug discovery
UR  - http://dx.doi.org/10.1101/814715
UR  - https://www.biorxiv.org/content/10.1101/814715v1
UR  - http://hdl.handle.net/10044/1/77033
ER  -
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