PXD046155 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A semi-synthesis platform for efficient production and exploration of didemnin-based drugs |
Description | In this study, we report the screening of the yield of didemnin B from 18 Tistrella strains we collected from different regions worldwide. Among them, one T. mobilis strain was further investigated due to its capability to produce the highest yield of didemnin B in a fermentation medium. To improve the productivity of the chosen strain, we performed 11 rounds of random mutagenesis/screening and optimised culture conditions. The resultant mutated strain produced over 500 mg/L of didemnin B in a 50-L fermentation tank. We further tested the strain in an industrial-scale fermentation tank (4,000-L), resulting in the production of didemnin B approximately 480 mg/L. Furthermore, we developed two simple and efficient chemical strategies for converting didemnin B to plitidepsin. One of the strategies involves a one-step synthetic route with over 90% overall yield. The modifications in the hydroxyl group of iso-statine (iso-Sta–OH) in didemnin B can greatly impact on its bioactivity. Therefore, we further synthesised 13 new didemnin B derivatives with modifications in iso-Sta–OH for studying the structure–activity relationships. In addition, 3 photo-affinity-based didemnin probes, bearing diazirine and alkyne groups, were prepared and employed in proteomic profiling studies, which allowed the deduction of binding proteins in the THP-1 cell line. Overall, our platform not only provides a practical and sustainable solution for producing the drug molecule plitidepsin, but also offers the opportunities to utilise the functions of didemnin derivatives. We envision that our platform can expedite the development of didemnin-based drugs. |
HostingRepository | PRIDE |
AnnounceDate | 2024-02-13 |
AnnouncementXML | Submission_2024-02-13_06:59:31.812.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Yun Ge |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetic acid derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-10-16 02:07:22 | ID requested | |
⏵ 1 | 2024-02-13 06:59:32 | announced | |
Publication List
Keyword List
submitter keyword: didemin, photo-affinity labeling |
Contact List
Yun Ge |
contact affiliation | 1. Institute of Chemical Biology, Shenzhen Bay Laboratory, 518107 Shenzhen, China; 2. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China |
contact email | geyun@szbl.ac.cn |
lab head | |
Yun Ge |
contact affiliation | Institute of Chemical Biology, Shenzhen Bay Laboratory |
contact email | geyun@szbl.ac.cn |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046155
- Label: PRIDE project
- Name: A semi-synthesis platform for efficient production and exploration of didemnin-based drugs