PXD047663

PXD047663 is an original dataset announced via ProteomeXchange.

Title	A polyketide-based biosynthetic platform for diols, amino alcohols and hydroxyacids
Description	Modular polyketide synthases (PKSs) have been proposed as promising megasynthases for retrobiosynthesis because of their fitness for rational carbon skeleton design. However, over the last three decades, all engineered PKSs produce carboxylic acids via terminal thioesterase (TE), which significantly narrows available chemical scope. We proposed the possibility of expanding PKS chemical diversity via terminal thioreductase (TR) engineering, and comprehensively characterised PKS TRs as NADPH-dependent enzymes to terminate polyketides with aldehyde. These aldehyde products can be readily converted to industrially valuable alcohols and amines, demonstrated by an engineered rimocidin PKS-TR producing 1,3-butanediol, 1,3-pentanediol, and 1,3-hexanediol with a total titer of 1008 mg/L in Streptomyces albus, or producing 554 mg/L 1-amino-3-alcohols via post-PKS transamination, both in shake flasks. Furthermore, efficient control of the product profile was achieved by coenzyme A (CoA) substrate regulation, as elevating butyryl-CoA level resulted in 1,3-hexanediol product ratio increased from 11% to 77%. We also demonstrated that PKS-TR can produce biosynthetically challenging branched-chain diols, culminating in production of 166 mg/L branched-chain 2-methyl-1,3-diols via acyltransferase exchange.
HostingRepository	PanoramaPublic
AnnounceDate	2024-12-17
AnnouncementXML	Submission_2024-12-17_10:27:09.612.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Chris Petzold
SpeciesList	scientific name: Streptomyces; NCBI TaxID: 1883;
ModificationList	No PTMs are included in the dataset
Instrument	6460 Triple Quadrupole LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-08 14:07:24	ID requested
⏵ 1	2024-12-17 10:27:10	announced

Dataset with its publication pending

submitter keyword: Metabolic engineering, polyketide synthase, PKS, 1, 3-butanediol, P-pant ejection assay, Streptomyces albus

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