Chemical proteomics techniques and their perspective enabling roles in quantitative engineering biology

Abstract

<p>Quantitative engineering biology, which uses tools to modify cells for various purposes, is a rapidly emerging interdisciplinary field at the frontier of current biological research. The technology lends itself to many diverse applications, ranging from biomedical uses such as vaccine development, engineered tissue and diagnostics, to industrial uses in numerous sectors including but not limited to agriculture, textiles, and bioenergy. Engineering biologists use rational design to assemble different biological components such as genes, promoters and other regulatory elements to produce genetic circuits with a wide range of innovative functions. To develop a novel circuit, engineering biologists use an iterative strategy of Design-Build-Test-Learn-Redesign, typically cycling through several iterations and optimizations before the final goal is achieved. Once the genetic circuit has successfully been engineered, it is inserted into cells that have been synthetically simplified to only contain essential genes. These basic cells are called chassis cells. They act as the host cell for the genetic circuit, allowing for the creation of many different types of engineered systems that are able to precisely perceive and respond to a variety of environments. By employing this rational design approach, engineering biologists have successfully created vital life-saving technologies like anti-tumor bacteria and virus. Proteomics is an essential tool in quantitative engineering biology. Proteins are the functional elements of almost all biological processes and engineered organisms are no exception. The ability to observe protein expression is necessary for understanding the working mechanism of the engineered organisms as well as the molecular interactions between the organisms and their surroundings. Quantitative proteomics provides a high-throughput way to study the spatio-temporal dynamics in the engineered organisms and their environments. However, classical proteomics lacks the ability to easily distinguish the newly synthesized proteome from the accumulated proteome, which is essential to proteome dynamics studies. Fortunately, chemical proteomics provides new possibilities for labeling and quantifying proteome dynamics. It is quickly becoming an essential tool for the functional characterization and mechanism discovery of newly-engineered organisms. Innovative chemical biology tools, such as unnatural amino acids and bio-orthogonal chemistry, along with the emergence of high-resolution mass spectrometry, have contributed to the incredible rise in popularity of chemical proteomics. These new methods have the unique ability to reveal the spatio-temporal dynamics of the engineered organisms' proteome in complex environments. Chemical proteomics is an indispensable technique to explore how engineered cells function in their host organisms. Furthermore, chemical proteomics allows us to develop effective methods for the complex functional studies required for quantitative engineering biology research. Here, we review the potential applications of chemical proteomics in quantitative engineering biology.</p>