PXD025067 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A microbial supply chain for production of anti-cancer drug vinblastine |
Description | Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine. As MIAs are difficult to chemically synthesize, the world’s supply chain for vinblastine relies on low-yielding extractions of precursors vindoline and catharanthine from the plant Catharanthus roseus, followed by chemical coupling and reduction to form vinblastine. Here, we demonstrate de novo microbial biosynthesis of vindoline and catharanthine from renewable feedstocks such as simple sugar and amino acids using highly engineered yeast. The study showcases the longest biosynthetic pathway refactored into a microbial cell factory to date, including 29 enzymatic steps from the yeast native metabolite geranyl pyrophosphate to catharanthine and vindoline. We made 44 genetic edits to yeast that include expression of 35 heterologous genes from plants as well as deletions, knock-downs, and overexpression of 10 yeast genes or variants thereof to improve the precursor supply. Finally, we demonstrate one-step in vitro vinblastine production using chemical coupling and reduction of vindoline and catharanthine. Not only is the yeast a scalable platform for production of vinblastine, it is also a platform for production of more than 2,000 different natural and new-to-nature MIAs. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:35:41.441.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Tune Wulff |
SpeciesList | scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-03-29 06:48:22 | ID requested | |
1 | 2022-08-21 07:57:04 | announced | |
2 | 2023-11-14 08:35:12 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2023-11-14 08:35:41 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Yeast synthetic biology, monoterpene indole alkaloids, natural products |
Contact List
Michael K. Jensen |
contact affiliation | Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark |
contact email | mije@biosustain.dtu.dk |
lab head | |
Tune Wulff |
contact affiliation | Technical University of Denmark, Novo Nordisk Foundation Center for Biosustainability |
contact email | tuwu@biosustain.dtu.dk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD025067
- Label: PRIDE project
- Name: A microbial supply chain for production of anti-cancer drug vinblastine