Peptide and Protein Building Blocks for Synthetic Biology: From Programming Biomolecules to Self-Organized Biomolecular Systems

• Published in: ACS chemical biology Vol. 3; no. 1; pp. 38 - 50
• Main Authors: Bromley, Elizabeth H. C, Channon, Kevin, Moutevelis, Efrosini, Woolfson, Derek N
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.01.2008
• Subjects: Amino Acids - chemistry; Models, Molecular; Nanostructures - chemistry; Peptides - chemistry; Protein Conformation; Protein Engineering; Proteins - chemistry; Tectons: Molecular components usually built via the polymerization of basic units and programmed to fold and/or assemble further to prescribed 3D structures; Functional assemblies: Higher-order associations of self-assembled units that confer complex structures or functions; Basic units: Small natural or synthetic molecular building blocks; Synthetic-biology space: A hierarchy of the above components; Self-assembled units: Combinations of tectons that adopt defined reproducible structures; Systems: Collections of functional assemblies that can perform multiple/complex chemical reactions. These are usually encapsulated, but they do not necessarily need to be; Synthetic biology: The attempt to understand nature through mimicry, and to create new functional bio-inspired systems; Path: A route through synthetic-biology space, for example, from a basic unit, or some other “sensible” starting point, toward an organized and/or functional system
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/cb700249v

There are several approaches to creating synthetic-biological systems. Here, we describe a molecular-design approach. First, we lay out a possible synthetic-biology space, which we define with a plot of complexity of components versus divergence from nature. In this scheme, there are basic units, which range from natural amino acids to totally synthetic small molecules. These are linked together to form programmable tectons, for example, amphipathic α-helices. In turn, tectons can interact to give self-assembled units, which can combine and organize further to produce functional assemblies and systems. To illustrate one path through this vast landscape, we focus on protein engineering and design. We describe how, for certain protein-folding motifs, polypeptide chains can be instructed to fold. These folds can be combined to give structured complexes, and function can be incorporated through computational design. Finally, we describe how protein-based systems may be encapsulated to control and investigate their functions.