PXD025067-1

PXD025067 is an original dataset announced via ProteomeXchange.

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	2022-08-21
AnnouncementXML	Submission_2022-08-21_07:57:04.014.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

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.

10.1038/S41586-022;

submitter keyword: Yeast synthetic biology, natural products, monoterpene indole alkaloids,

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

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PRIDE project URI

• PRIDE
  1. PXD025067
     1. Label: PRIDE project
     2. Name: A microbial supply chain for production of anti-cancer drug vinblastine