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Using Directed Evolution in the Lab

Scientist on February 13, 2014
Directed evolution has been used to create more cost-effective and energy-efficient biofuels.

This is the third and final post of a series (part 1 and part 2) on directed evolution.

What do protein engineers actually produce using directed evolution? Truth be told, we would need many, many more posts to go through all the amazing new proteins that scientists and engineers have created. We’ll talk about just three of them.

Evolving Better Biofuels

Discussion abounds in the media on how to reduce our reliance on imported oil as a source of energy. Biofuels such as corn-based ethanol are a viable alternative, but they are costly to produce, and corn-based ethanol in particular doesn’t reduce greenhouse gas emissions by much. Ideally, we would use plants that aren’t used as food crops for our source of biofuels, but breaking down cellulose – the tough polysaccharide that is the main component of a plant’s cell wall – is complicated and expensive. Enter directed evolution! Frances Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering, and Biochemistry at CalTech, used directed evolution to engineer enzymes that break down cellulose cheaply and efficiently.1 In addition, Arnold’s research team made enzymes that break down the sugars from cellulose to form isobutanol, which is more versatile than ethanol – it can be converted to aviation fuel, diesel, and plastics.

Thank Directed Evolution for Your Clean Laundry

The protease subtilisin is a commercially important enzyme; it is often used as an additive in laundry detergent. Enzymes used for industrial tasks such as laundry often need to overcome many challenges to function optimally: subtilisin must be active at high temperatures, high pH, and show stability in a variety of solvents. While it’s possible to improve one property of an enzyme using random mutagenesis, it’s often at the cost of another critical function. Researchers used directed evolution to get around this problem: by recombining the gene encoding a different commercial protease with subtilisin gene fragments, they were able to engineer a new version of subtilisin that is thermostable, solvent stable, and functions between pH 5 and 10.2

Using Directed Evolution in Drug Design

An international team of researchers led by Dr. Nicholas Brindle of the University of Leicester used directed evolution to design a novel drug against angiopoetin-2, or Ang2, that could possibly help treat atherosclerosis, sepsis, and cancer.3 Increased expression of Ang2 is linked to a variety of diseases, and is thus an ideal candidate for therapy by ligand trap. Ligand traps are drugs used to sequester ligands away from their target receptors. Unfortunately, the main receptor for Ang2, Tie2, also binds the related ligand Ang1, a protective protein that helps suppress inflammation. The challenge for the researchers was to come up with a very specific ligand trap that would bind to Ang2, but not Ang1. Using directed evolution, Brindle and colleagues introduced the Tie2 gene into B cells, and then selected for the version of Tie2 that bound Ang2 over Ang1. In this way, they were able to successfully generate an Ang2-specific ligand trap.

Directed evolution has the potential to change our lives in so many different ways. If you would like to engineer a brand-new protein, Scientist can connect you with several vendors offering directed evolution services who can help with each step of this amazing technique.

  1. Woo, MY. Researcher tries directed evolution to craft better biofuels.
  2. Yuan, L, et al. Laboratory-Directed Protein Evolution. Microbiol Mol Biol Rev 69(3): 373-392. September 2005.
  3. Brindle NPJ, et al. Directed Evolution of an Angiopoietin-2 Ligand Trap by Somatic Hypermutation and Cell Surface Display. J Biol Chem, 288(46):33205-12