PXD069956

PXD069956 is an original dataset announced via ProteomeXchange.

Title	Engineering an Extremely Hybrid PKS for Adipic Acid Production
Description	Polyketide synthases (PKSs) are modular enzymes with exceptional potential as biocatalysts for producing non-native compounds. Here, we report the first PKS-based pathway for adipic acid (AA), an industrial monomer for nylon production, by engineering one of the most extensively hybridized PKS systems to date. Using a retrobiosynthetic approach, we identified EtnB, a succinyl-CoA loading module that uniquely retains the terminal carboxyl group, enabling access to dicarboxylic polyketide products, rarely produced by canonical PKSs. EtnB was coupled to a fully reducing extension module through an engineered communication linker, which improved ACP–KS interactions, enhanced titers, and demonstrated selective S-CoA loading in vivo. This construct integrates genes from five organisms, seven PKS modules joined across six non-natural junctions, and functions in both Escherichia coli and Pseudomonas putida. Additional engineering that included AT domain swaps, optimization of extender unit supply, and host strain metabolic rewiring further improved AA titers into the low mg/L range. Together, this work demonstrates that highly chimeric PKSs can be rendered functional through rational design, expands the PKS toolkit with a carboxyl-retaining loading module, and establishes a versatile platform for engineering diacids and other non-canonical products through PKS pathways.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_04:24:09.310.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christopher Petzold
SpeciesList	scientific name: Pseudomonas putida KT2440; NCBI TaxID: NEWT:160488;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-27 16:43:09	ID requested
⏵ 1	2026-09-07 04:24:10	announced

Klass SH, Wang Z, Lanclos N, Wesselkamper M, Li C, Baerwald J, Pearson A, Thomas M, Hu W, Schmidt M, Chen Y, Gin JW, Petzold CJ, Keasling JD, Engineering an Extremely Hybrid PKS for Adipic Acid Production. ACS Synth Biol, 15(7):2887-2899(2026) [pubmed]

10.1021/acssynbio.5c00972;

submitter keyword: Hybrid PKS, Polyketide Synthase,Adipic acid, P. putida,JBEI, E. coli

Christopher Petzold
contact affiliation	Staff Scientist Biological Systems & Engineering Division Lawrence Berkeley National Laboratory Berkeley CA 94720
contact email	cjpetzold@lbl.gov
lab head
Christopher Petzold
contact affiliation	Lawrence Berkeley National Laboratory
contact email	cjpetzold@lbl.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069956
     1. Label: PRIDE project
     2. Name: Engineering an Extremely Hybrid PKS for Adipic Acid Production