PXD046155

PXD046155 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-16 02:07:22	ID requested
⏵ 1	2024-02-13 06:59:32	announced

10.1002/ANIE.202318784;

submitter keyword: didemin, photo-affinity labeling

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD046155

PRIDE project URI

• PRIDE
  1. PXD046155
     1. Label: PRIDE project
     2. Name: A semi-synthesis platform for efficient production and exploration of didemnin-based drugs