Protein engineering: opportunities and challenges
- 802 Downloads
The extraordinary properties of natural proteins demonstrate that life-like protein engineering is both achievable and valuable. Rapid progress and impressive results have been made towards this goal using rational design and random techniques or a combination of both. However, we still do not have a general theory on how to specify a structure that is suited to a target function nor can we specify a sequence that folds to a target structure. There is also overreliance on the Darwinian blind search to obtain practical results. In the long run, random methods cannot replace insight in constructing life-like proteins. For the near future, however, in enzyme development, we need to rely on a combination of both.
KeywordsProtein engineering Directed evolution Enzymes
The authors thank Douglas Axe for his helpful criticism and for revising the text.
- Aharoni A, Gaidukov L, Khersonsky O, McQ Gould S, Roodveldt C, Tawfik DS (2005) The ‘evolvability’ of promiscuous protein functions. Nat Genet 37:73–76Google Scholar
- Arnold (2007) Directed enzyme evolution http://www.che.caltech.edu/groups/fha/directed_evolution.html
- Chothia C, Lesk AM (1986) The relation between the divergence of sequence and structure in proteins. EMBO J 5:823–826Google Scholar
- McLachlan AD (1987) Gene duplication and the origin of repetitive protein structures. In: Cold Spring Harbor symposium on quantitative biology, vol. LII. Cold Spring Harbor laboratory, Cold Spring Harbor, p. 411–420Google Scholar
- Ohno S (1970) Evolution by gene duplication. Springer, Berlin Heidelberg New YorkGoogle Scholar
- Williams JC, Zeelen JP, Neubauer G, Vriend G, Backmann J, Michels PAM, Lambeir, A-M, Wierenga RK (1999) Structural and mutagenesis studies of leishmania triosephosphate isomerase: a point mutation can convert a mesophilic enzyme into a superstable enzyme without losing catalytic power. Prot Eng 12:243–250CrossRefGoogle Scholar