Exploring and Expanding the Protein Universe with Non-Canonical Amino Acids

  • 7,252

    Total Downloads

  • 38k

    Total Views and Downloads

Download PDFDownload EPUB

Submit your idea

Select the journal/section where you want your idea to be submitted:

Submit your manuscript summarySubmit your manuscript

About this Research Topic

Submission closed

Background

The site-specific incorporation of unnatural or non-canonical amino acids (ncAAs) into proteins is a universally important tool for systems bioengineering at the interface of chemistry, biology, and biotechnology. The synergistic use of ncAA and related technologies (e.g. Xeno nucleic acids) should enable:
i) New opportunities to manipulate, design and elucidate protein structure, dynamics, and function.
ii) A deeper understanding of natural and evolved translational systems and their importance for artificial biology.
iii) The synthesis of novel biopolymers, creating a solid basis for synthetic cells, which is also an important technology in the production of new classes of medically relevant protein-based scaffolds.
Research on reprogrammed protein translation has now reached an experimental and intellectual maturity: more than 200 ncAA (i.e. more than ten times larger variety than standard amino acids) have been introduced into proteins using different routes: genetic code expansion (GCE), selective pressure incorporation (SPI), chemical mutagenesis, protein semi-synthesis, and peptide synthesis.

Although the field is almost 30-year-old, has become terminologically established, and is methodologically broad, there is still a strong need to overcome the bottlenecks of traditional approaches to producing high-quality chemically modified polypeptides. The majority of ncAAs in practice are the chemical variants of amino acid side-chains while there are very few studies with basic building blocks having alternative backbones (inverted chirality, chemical modifications of the alpha-carbon atom, etc.) There is also a lack of systematic research on the biological consequences of ncAA incorporation and the molecular mechanism that determine the effectiveness of orthogonal translation. Therefore, we believe that future developments in the ncAA field must involve:
(a) Protein engineering, including rational design and directed evolution assisted by artificial intelligence.
(b) Reprogrammed protein translation with orthogonal sense codon reassignment.
(c) Metabolic engineering, including cofactor engineering.
(d) Adaptive laboratory evolution and genome engineering/editing, for codon reassignment with the option of integrating expanded genetic alphabets to create synthetic cells with altered genetic codes. The long-term mission should be to convert the expansion of the genetic code/genetic code engineering into a routine method for every laboratory and every industry.

On a more practical level, this Research Topic is based on 3 basic pillars: (i) genetic code engineering as an approach, tool, and technology for life sciences, (ii) a broad range of applications of ncAAs, (iii) an active approach to synthetic cells (life). Specific themes include but are not limited to:
● Integrative/hybrid approaches to incorporate ncAA (e.g. GCE-SPI)
● Novel applications of ncAA in any area (bio-orthogonal chemistry, drug discovery, etc.)
● Augmenting the ncAA chemical space to cover new side-chains and backbones (e.g. D-aa)
● Robust procedures to site-specifically install multiple (>2) ncAA
● Methods to incorporate ncAA in multiple proteins or even whole proteomes

We encourage submissions from both “developers” of these technologies as well as “users”. In silico, in vitro, and in vivo studies are all welcome. Regular papers, short communications, or reviews are equally acceptable.

Dr. Kensaku Sakamoto receives funding from a company relating to the subject of this Research Topic

Keywords: Non-Standard Amino Acids, Protein Structure, Protein Dynamics, Protein Functions, Structure-Function, Protein Engineering

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.

Topic editors

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and they fall under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

      In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

     

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

     

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

     

Participating Journals

Impact

  • 38kTopic views
  • 29kArticle views
  • 7,252Article downloads
View impact