page_title: Synthetic biology
section_title: Designed proteins
hierarchical_section_title: Synthetic biology / Applications / Designed proteins
caption_attribution_description: English: Ribbon diagram of the Top 7, computationally designed protein, based on the structure PDB id: 1QYS. The fold corresponds to one not seen previously on nature. For more information see: Kuhlman, Brian, et al. "Design of a novel globular protein fold with atomic-level accuracy." Science 302.5649 (2003): 1364-1368.
context_page_description: Synthetic biology is a multidisciplinary area of research that seeks to create new biological parts, devices, and systems, or to redesign systems that are already found in nature.
  It is a branch of science that encompasses a broad range of methodologies from various disciplines, such as biotechnology, genetic engineering, molecular biology, molecular engineering, systems biology, membrane science, biophysics, chemical and biological engineering, electrical and computer engineering, control engineering and evolutionary biology.
  Due to more powerful genetic engineering capabilities and decreased DNA synthesis and sequencing costs, the field of synthetic biology is rapidly growing. In 2016, more than 350 companies across 40 countries were actively engaged in synthetic biology applications; all these companies had an estimated net worth of $3.9 billion in the global market.
context_section_description: Natural proteins can be engineered, for example, by directed evolution, novel protein structures that match or improve on the functionality of existing proteins can be produced. One group generated a helix bundle that was capable of binding oxygen with similar properties as hemoglobin, yet did not bind carbon monoxide. A similar protein structure was generated to support a variety of oxidoreductase activities  while another fromed a structurally and sequentially novel ATPase. Another group generated a family of G-protein coupled receptors that could be activated by the inert small molecule clozapine N-oxide but insensitive to the native ligand, acetylcholine; these receptors are known as DREADDs. Novel functionalities or protein specificity can also be engineered using computational approaches.  One study was able to use two different computational methods – a bioinformatics and molecular modeling method to mine sequence databases, and a computational enzyme design method to reprogram enzyme specificity. Both methods resulted in designed enzymes with greater than 100 fold specificity for production of longer chain alcohols from sugar.
  Another common investigation is expansion of the natural set of 20 amino acids. Excluding stop codons, 61 codons have been identified, but only 20 amino acids are coded generally in all organisms. Certain codons are engineered to code for alternative amino acids including: nonstandard amino acids such as O-methyl tyrosine; or exogenous amino acids such as 4-fluorophenylalanine. Typically, these projects make use of re-coded nonsense suppressor tRNA-Aminoacyl tRNA synthetase pairs from other organisms, though in most cases substantial engineering is required.
  Other researchers investigated protein structure and function by reducing the normal set of 20 amino acids. Limited protein sequence libraries are made by generating proteins where groups of amino acids may be replaced by a single amino acid. For instance, several non-polar amino acids within a protein can all be replaced with a single non-polar amino acid . One project demonstrated that an engineered version of Chorismate mutase still had catalytic activity when only 9 amino acids were used.
  Researchers and companies practice synthetic biology to synthesize industrial enzymes with high activity, optimal yields and effectiveness. These synthesized enzymes aim to improve products such as detergents and lactose-free dairy products, as well as make them more cost effective. The improvements of metabolic engineering by synthetic biology is an example of a biotechnological technique utilized in industry to discover pharmaceuticals and fermentive chemicals. Synthetic biology may investigate modular pathway systems in biochemical production and increase yields of metabolic production. Artificial enzymatic activity and subsequent effects on metabolic reaction rates and yields may develop "efficient new strategies for improving cellular properties ... for industrially important biochemical production".
caption: The Top7 protein was one of the first proteins designed for a fold that had never been seen before in nature[81]
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