Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis
Abstract Background Among naturally occurring small molecules, tRNA-derived cyclodipeptides are a class that have attracted attention for their diverse and desirable biological activities. However, no tools are available to link cyclodipeptide synthases identified within prokaryotic genome sequences...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-018-4435-1 |
| _version_ | 1830478600021737472 |
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| author | Michael A. Skinnider Chad W. Johnston Nishanth J. Merwin Chris A. Dejong Nathan A. Magarvey |
| author_facet | Michael A. Skinnider Chad W. Johnston Nishanth J. Merwin Chris A. Dejong Nathan A. Magarvey |
| author_sort | Michael A. Skinnider |
| collection | DOAJ |
| description | Abstract Background Among naturally occurring small molecules, tRNA-derived cyclodipeptides are a class that have attracted attention for their diverse and desirable biological activities. However, no tools are available to link cyclodipeptide synthases identified within prokaryotic genome sequences to their chemical products. Consequently, it is unclear how many genetically encoded cyclodipeptides represent novel products, and which producing organisms should be targeted for discovery. Results We developed a pipeline for identification and classification of cyclodipeptide biosynthetic gene clusters and prediction of aminoacyl-tRNA substrates and complete chemical structures. We leveraged this tool to conduct a global analysis of tRNA-derived cyclodipeptide biosynthesis in 93,107 prokaryotic genomes, and compared predicted cyclodipeptides to known cyclodipeptide synthase products and all known chemically characterized cyclodipeptides. By integrating predicted chemical structures and gene cluster architectures, we created a unified map of known and unknown genetically encoded cyclodipeptides. Conclusions Our analysis suggests that sizeable regions of the chemical space encoded within sequenced prokaryotic genomes remain unexplored. Our map of the landscape of genetically encoded cyclodipeptides provides candidates for targeted discovery of novel compounds. The integration of our pipeline into a user-friendly web application provides a resource for further discovery of cyclodipeptides in newly sequenced prokaryotic genomes. |
| first_indexed | 2024-12-21T16:32:11Z |
| format | Article |
| id | doaj.art-4161aa238ce542d18449758c8ca3706a |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-21T16:32:11Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-4161aa238ce542d18449758c8ca3706a2022-12-21T18:57:20ZengBMCBMC Genomics1471-21642018-01-0119111110.1186/s12864-018-4435-1Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesisMichael A. Skinnider0Chad W. Johnston1Nishanth J. Merwin2Chris A. Dejong3Nathan A. Magarvey4Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster UniversityDepartment of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster UniversityDepartment of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster UniversityDepartment of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster UniversityDepartment of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster UniversityAbstract Background Among naturally occurring small molecules, tRNA-derived cyclodipeptides are a class that have attracted attention for their diverse and desirable biological activities. However, no tools are available to link cyclodipeptide synthases identified within prokaryotic genome sequences to their chemical products. Consequently, it is unclear how many genetically encoded cyclodipeptides represent novel products, and which producing organisms should be targeted for discovery. Results We developed a pipeline for identification and classification of cyclodipeptide biosynthetic gene clusters and prediction of aminoacyl-tRNA substrates and complete chemical structures. We leveraged this tool to conduct a global analysis of tRNA-derived cyclodipeptide biosynthesis in 93,107 prokaryotic genomes, and compared predicted cyclodipeptides to known cyclodipeptide synthase products and all known chemically characterized cyclodipeptides. By integrating predicted chemical structures and gene cluster architectures, we created a unified map of known and unknown genetically encoded cyclodipeptides. Conclusions Our analysis suggests that sizeable regions of the chemical space encoded within sequenced prokaryotic genomes remain unexplored. Our map of the landscape of genetically encoded cyclodipeptides provides candidates for targeted discovery of novel compounds. The integration of our pipeline into a user-friendly web application provides a resource for further discovery of cyclodipeptides in newly sequenced prokaryotic genomes.http://link.springer.com/article/10.1186/s12864-018-4435-1Cyclodipeptide synthaseGenome miningSecondary metabolism |
| spellingShingle | Michael A. Skinnider Chad W. Johnston Nishanth J. Merwin Chris A. Dejong Nathan A. Magarvey Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis BMC Genomics Cyclodipeptide synthase Genome mining Secondary metabolism |
| title | Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis |
| title_full | Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis |
| title_fullStr | Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis |
| title_full_unstemmed | Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis |
| title_short | Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis |
| title_sort | global analysis of prokaryotic trna derived cyclodipeptide biosynthesis |
| topic | Cyclodipeptide synthase Genome mining Secondary metabolism |
| url | http://link.springer.com/article/10.1186/s12864-018-4435-1 |
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