Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium
Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/21/6/367 |
| _version_ | 1797593737937813504 |
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| author | Min Cheol Kim Jaclyn M. Winter Reiko Cullum Alexander J. Smith William Fenical |
| author_facet | Min Cheol Kim Jaclyn M. Winter Reiko Cullum Alexander J. Smith William Fenical |
| author_sort | Min Cheol Kim |
| collection | DOAJ |
| description | Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb <i>mld</i> biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis. |
| first_indexed | 2024-03-11T02:13:44Z |
| format | Article |
| id | doaj.art-b48ecf6564b2451bb9ac433af23ae50c |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-11T02:13:44Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-b48ecf6564b2451bb9ac433af23ae50c2023-11-18T11:22:54ZengMDPI AGMarine Drugs1660-33972023-06-0121636710.3390/md21060367Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived BacteriumMin Cheol Kim0Jaclyn M. Winter1Reiko Cullum2Alexander J. Smith3William Fenical4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, Skaggs School of Pharmacy and Pharmaceutical Sciences, Moores Comprehensive Cancer Center, University of California, La Jolla, San Diego, CA 92093, USADepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USACenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, Skaggs School of Pharmacy and Pharmaceutical Sciences, Moores Comprehensive Cancer Center, University of California, La Jolla, San Diego, CA 92093, USACenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, Skaggs School of Pharmacy and Pharmaceutical Sciences, Moores Comprehensive Cancer Center, University of California, La Jolla, San Diego, CA 92093, USACenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, Skaggs School of Pharmacy and Pharmaceutical Sciences, Moores Comprehensive Cancer Center, University of California, La Jolla, San Diego, CA 92093, USAMarinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb <i>mld</i> biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis.https://www.mdpi.com/1660-3397/21/6/367macrolactonenatural product structure elucidationbioinformaticsgenome miningmodular type I polyketide synthase |
| spellingShingle | Min Cheol Kim Jaclyn M. Winter Reiko Cullum Alexander J. Smith William Fenical Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium Marine Drugs macrolactone natural product structure elucidation bioinformatics genome mining modular type I polyketide synthase |
| title | Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium |
| title_full | Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium |
| title_fullStr | Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium |
| title_full_unstemmed | Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium |
| title_short | Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium |
| title_sort | expanding the utility of bioinformatic data for the full stereostructural assignments of marinolides a and b 24 and 26 membered macrolactones produced by a chemically exceptional marine derived bacterium |
| topic | macrolactone natural product structure elucidation bioinformatics genome mining modular type I polyketide synthase |
| url | https://www.mdpi.com/1660-3397/21/6/367 |
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