PXD024976

PXD024976 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	PanoramaPublic
AnnounceDate	2022-09-09
AnnouncementXML	Submission_2022-09-09_11:33:00.316.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Chris Petzold
SpeciesList	scientific name: Saccharomyces cerevisiae; NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	6460 Triple Quadrupole LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-24 20:34:55	ID requested
⏵ 1	2022-09-09 11:33:01	announced

Zhang J, Hansen LG, Gudich O, Viehrig K, Lassen LMM, Schr, ü, bbers L, Adhikari KB, Rubaszka P, Carrasquer-Alvarez E, Chen L, D'Ambrosio V, Lehka B, Haidar AK, Nallapareddy S, Giannakou K, Laloux M, Arsovska D, J, ø, rgensen MAK, Chan LJG, Kristensen M, Christensen HB, Sudarsan S, Stander EA, Baidoo E, Petzold CJ, Wulff T, O'Connor SE, Courdavault V, Jensen MK, Keasling JD, A microbial supply chain for production of the anti-cancer drug vinblastine. Nature, 609(7926):341-347(2022) [pubmed]

submitter keyword: Synthetic biology, Vinblastine, Metabolic engineering

Chris Petzold
contact affiliation	Lawrence Berkeley National Laboratory
contact email	cjpetzold@lbl.gov
lab head
Chris Petzold
contact affiliation	Lawrence Berkeley National Laboratory
contact email	cjpetzold@lbl.gov
dataset submitter

Panorama Public dataset URI