Synthetic biology approaches for evolving engineered multi-enzyme pathways and nano-complexes.

Abstract

De novo pathway design represents a cutting-edge synthetic biology approach to the synthesis of high-value chemicals using micro-organisms to convert sustainable bio-feedstocks. Most research has focussed on transplanting existing pathways to natural products, from complex to simple organisms, our focus is to create entire de novo pathways from unrelated enzymes to synthesise chemicals not already found in nature. We recently created a de novo pathway with two enzymes co-expressed for the synthesis of chiral amino-diols in E.coli [Ingram 2007] and improved it using an independently engineered enzyme variant [Rios-Solis 2011].  This project aims to embed our de novo designed pathway within artificial multi-enzyme nano-complexes in a highly novel manner. 

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References:
[1]

C. U. Ingram, M. Bommer, M. E. B. Smith, P. A. Dalby, J. M. Ward, H. C. Hailes, and G. J. Lye, (2007) Biotech. Bioeng. 96, 559-569.

[2]

L. Rios-Solis, M. Halim, A. Cázares, P. Morris, J. M. Ward, H.C. Hailes, P.A. Dalby, F. Baganz, G. J. Lye (2011) Biocatalysis and Biotransformation.29(5):192-203.

[3]

Hibbert, E.G., Senussi, T., Costelloe, S.J., Lei, W., Smith, M.E.B., Ward, J.M., Hailes, H.C., and Dalby, P.A. (2007) Journal of Biotechnology 131, 425-432. Directed evolution of transketolase activity on non-phosphorylated substrates.

[4]

Smith, M.E.B., Hibbert, E.G., Jones, A.B., Dalby, P.A, and Hailes, H.C. (2008) Adv Syn Catal 350, 2631-2638. Enhancing and reversing the enantioselectivity of E. coli transketolase via single point mutations.

[5]

Cázares, A., Galman, J.L., Crago, L.G., Smith, M.E.B., Strafford, J., Ríos-Solís, L., Lye, G.J., Dalby, P.A., Hailes, H.C.  (2010) Organic & Biomolecular Chemistry. 8(6), 1301-1309. Non-alpha-hydroxylated aldehydes with evolved transketolase enzymes


Biological Areas:

Chemical Biology
Biotechnology

BBSRC Area:

Molecules, cells and industrial biotechnology