Advanced Genetic Strategies for Recombinant Protein Expression in Bacteria

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Background

Bacterial expression system is the preferred protein production system for both scientific investigation and commercial development, for its simplicity, ease-of-use, speed and cost. It has made tremendous contributions to protein science (structure-function relationship and mechanistic study) and protein applications (enzymes, therapeutics, diagnostics, biomaterials and synthetic biology). Worthy of a highlight, almost a quarter of the biopharmaceuticals approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) from 2004 to 2013 were produced with bacterial expression systems. Although widely used for decades in laboratories and industries worldwide, the field of bacterial expression system remains vibrant, being constantly fueled with advancement, innovation and creativity. From the recombinant human insulin production in the 1970s till the recent applications as synthetic biology chasses, we continue to witness advancements in bacterial strain and genetic construct development to further improve the type, the quantity and the quality of the recombinant proteins produced. Therefore, an update and a consolidation of existing knowledge are timely and necessary to further advance the field and to benefit the entire protein science community.

The field of bacterial protein expression is developing so rapidly that it is difficult for us to keep track of key developments and latest technologies. On top of that, some laboratories have developed in-house protein expression systems or expression protocols, which will benefit others when shared through an appropriate channel. More often than not, a slight change to an existing method or a small modification to a genetic element could make a big difference to protein yield or protein quality. These tricks are equally important compared to new techniques. We strongly believe that the protein community will benefit massively from a special issue that is dedicated entirely to the topic of bacterial protein expression. Not only does it serve as a one-stop shop for information and methodologies relevant to this research area, it establishes a platform for scientific exchange and discussion. This Research Topic is therefore created to:
• summarize recent advances in the topic of bacterial protein expression
• advance the field of bacterial synthetic biology
• identify research opportunities and research gaps
• disseminate knowledge and techniques in this discipline
• stimulate thought, discussion, and debate to further advance and fully exploit bacterial protein expression systems
• create an integrated scientific network and promote research collaboration
• encourage continued research support and funding in this key research area

Recombinant protein expression begins with choosing the right expression host. The choice of host directly affects the yield, the location (intracellular, extracellular, surface-tethered), and the quality (soluble, insoluble, post-translationally modified) of the resultant recombinant protein. All these four aspects (host, yield, location and quality) are key considerations whilst developing a downstream processing strategy for protein isolation, purification and formulation. This Research Topic focuses mainly on the genetic strategies to improve the performance of protein expression host, increase protein yield, alter protein localization and enhance protein quality. Specific themes include, but are not limited to,
• Novel bacterial hosts for recombinant protein expression (e.g., Vibrio natriegens).
• Host engineering (e.g., CRISPR-assisted regulation)
• Expression vectors and selection strategies
• Codon optimization or engineering for protein expression in bacteria
• Optimization of genetic and regulatory elements (biological parts)
• Mechanism governing in vivo protein formation
• Signal peptides or fusion tags for protein localization and solubility
• Protein secretion from bacterial host
• Bacterial surface display of recombinant protein
• Chaperone
• Protein glycosylation in bacteria
• Other strategies for the production of ‘difficult-to-express’ proteins
We welcome contributions from both experimentalists and computational scientists, in the forms of original article, method, review, mini-review, opinion, as well as hypothesis & theory.

Keywords: Bacterial expression, Recombinant protein, Expression host, Expression vector, Protein secretion

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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