Strategies for protein synthetic biology

Nucleic Acids Res. 2010 May;38(8):2663-75. doi: 10.1093/nar/gkq139. Epub 2010 Apr 12.


Proteins are the most versatile among the various biological building blocks and a mature field of protein engineering has lead to many industrial and biomedical applications. But the strength of proteins-their versatility, dynamics and interactions-also complicates and hinders systems engineering. Therefore, the design of more sophisticated, multi-component protein systems appears to lag behind, in particular, when compared to the engineering of gene regulatory networks. Yet, synthetic biologists have started to tinker with the information flow through natural signaling networks or integrated protein switches. A successful strategy common to most of these experiments is their focus on modular interactions between protein domains or domains and peptide motifs. Such modular interaction swapping has rewired signaling in yeast, put mammalian cell morphology under the control of light, or increased the flux through a synthetic metabolic pathway. Based on this experience, we outline an engineering framework for the connection of reusable protein interaction devices into self-sufficient circuits. Such a framework should help to 'refacture' protein complexity into well-defined exchangeable devices for predictive engineering. We review the foundations and initial success stories of protein synthetic biology and discuss the challenges and promises on the way from protein- to protein systems design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA / chemistry
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Models, Molecular
  • Protein Engineering / methods*
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping*
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism
  • Signal Transduction


  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • DNA