Marine-derived microbes and molecules for drug discovery
Abstract Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have coll...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Inflammation and Regeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41232-022-00207-9 |
| _version_ | 1817968763414249472 |
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| author | Yoshimasa Tanaka Megumi Nishikawa Kaho Kamisaki Saki Hachiya Moeka Nakamura Takahiro Kuwazuru Susumu Tanimura Kiyoshi Soyano Kohsuke Takeda |
| author_facet | Yoshimasa Tanaka Megumi Nishikawa Kaho Kamisaki Saki Hachiya Moeka Nakamura Takahiro Kuwazuru Susumu Tanimura Kiyoshi Soyano Kohsuke Takeda |
| author_sort | Yoshimasa Tanaka |
| collection | DOAJ |
| description | Abstract Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein–protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies. |
| first_indexed | 2024-04-13T20:12:09Z |
| format | Article |
| id | doaj.art-c5173ffe1e174398bc8f7647c6db1483 |
| institution | Directory Open Access Journal |
| issn | 1880-8190 |
| language | English |
| last_indexed | 2024-04-13T20:12:09Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Inflammation and Regeneration |
| spelling | doaj.art-c5173ffe1e174398bc8f7647c6db14832022-12-22T02:31:48ZengBMCInflammation and Regeneration1880-81902022-06-0142111210.1186/s41232-022-00207-9Marine-derived microbes and molecules for drug discoveryYoshimasa Tanaka0Megumi Nishikawa1Kaho Kamisaki2Saki Hachiya3Moeka Nakamura4Takahiro Kuwazuru5Susumu Tanimura6Kiyoshi Soyano7Kohsuke Takeda8Center for Medical Innovation, Nagasaki UniversityDepartment of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki UniversityInstitute for East China Sea Research, Nagasaki UniversityDepartment of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki UniversityInstitute for East China Sea Research, Nagasaki UniversityDepartment of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki UniversityAbstract Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein–protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies.https://doi.org/10.1186/s41232-022-00207-9Autoimmune diseaseAutoinflammatory diseaseBiologicConventional drugMarine microbeMonoclonal antibody |
| spellingShingle | Yoshimasa Tanaka Megumi Nishikawa Kaho Kamisaki Saki Hachiya Moeka Nakamura Takahiro Kuwazuru Susumu Tanimura Kiyoshi Soyano Kohsuke Takeda Marine-derived microbes and molecules for drug discovery Inflammation and Regeneration Autoimmune disease Autoinflammatory disease Biologic Conventional drug Marine microbe Monoclonal antibody |
| title | Marine-derived microbes and molecules for drug discovery |
| title_full | Marine-derived microbes and molecules for drug discovery |
| title_fullStr | Marine-derived microbes and molecules for drug discovery |
| title_full_unstemmed | Marine-derived microbes and molecules for drug discovery |
| title_short | Marine-derived microbes and molecules for drug discovery |
| title_sort | marine derived microbes and molecules for drug discovery |
| topic | Autoimmune disease Autoinflammatory disease Biologic Conventional drug Marine microbe Monoclonal antibody |
| url | https://doi.org/10.1186/s41232-022-00207-9 |
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