Understanding the enzymatic factories that assemble microbial natural products

Abstract

Microbial natural products continue to be an important source of therapeutics such as antibiotics. Microbial natural products such as polyketides are biosynthesized by large enzyme assemblies, which function much like factory assembly lines to produce a core structure which is then modified by so called tailoring enzymes which can introduce a variety of functional groups. The aim of this project is to investigate a particular natural product pathway to elucidate both the catalytic function of the enzymes and the complex protein-protein interactions between them, which allows the assembly line to function.

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References:
[1]

Fischbach, M. A.; Walsh, C. T. (2006) Assembly-Line Enzymology for Polyketide and Non-ribosomal Peptide Antibiotics:  Logic, Machinery, and Mechanisms Chem. Rev. 106, 3468.

[2]

Winter, J. M.; Tang. Y. (2012) Synthetic biological approaches to natural product biosynthesis. Curr. Opin. Biotechnol.  23, 736.

[3]

Weissman, K. J.; Müller, R. (2008) Protein–Protein Interactions in Multienzyme Megasynthetases, ChemBioChem 9, 826.

[4]

Clardy, J.; Fischbach, M. A.; Walsh, C. T. (2006) New antibiotics from bacterial natural products Nat. Biotech. 24, 1541.


Biological Areas:

Chemical Biology
Microbiology

BBSRC Area:

Molecules, cells and industrial biotechnology