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Structure paper

TitleThe structure of a polyketide synthase bimodule core.
Journal, issue, pagesSci Adv, Vol. 8, Issue 38, Page eabo6918, Year 2022
Publish dateSep 23, 2022
AuthorsYves U Tittes / Dominik A Herbst / Solène F X Martin / Hugo Munoz-Hernandez / Roman P Jakob / Timm Maier /
PubMed AbstractPolyketide synthases (PKSs) are predominantly microbial biosynthetic enzymes. They assemble highly potent bioactive natural products from simple carboxylic acid precursors. The most versatile ...Polyketide synthases (PKSs) are predominantly microbial biosynthetic enzymes. They assemble highly potent bioactive natural products from simple carboxylic acid precursors. The most versatile families of PKSs are organized as assembly lines of functional modules. Each module performs one round of precursor extension and optional modification, followed by directed transfer of the intermediate to the next module. While enzymatic domains and even modules of PKSs are well understood, the higher-order modular architecture of PKS assembly lines remains elusive. Here, we visualize a PKS bimodule core using cryo-electron microscopy and resolve a two-dimensional meshwork of the bimodule core formed by homotypic interactions between modules. The sheet-like organization provides the framework for efficient substrate transfer and for sequestration of trans-acting enzymes required for polyketide production.
External linksSci Adv / PubMed:36129979 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.62 - 6.8 Å
Structure data

EMDB-14793, PDB-7zma:
Ketosynthase domain of module 4 from Brevibacillus Brevis orphan BGC11
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-14795, PDB-7zmd:
Ketosynthase domain of module 3 from Brevibacillus Brevis orphan BGC11
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-14945: K3DAK4 bimodule core of BGC11 from Brevibacillus brevis
PDB-7zsk: K3DAK4 bimodule core of BGC11 from Brevibacillus brevis.
Method: EM (single particle) / Resolution: 6.8 Å

PDB-7zm9:
Ketosynthase domain 3 of Brevibacillus Brevis orphan BGC11
Method: X-RAY DIFFRACTION / Resolution: 1.62 Å

PDB-7zmc:
Ketosynthase domain of module 4 from Brevibacillus Brevis orphan BGC11
Method: X-RAY DIFFRACTION / Resolution: 3.1 Å

PDB-7zmf:
Dehydratase domain of module 3 from Brevibacillus Brevis orphan BGC11
Method: X-RAY DIFFRACTION / Resolution: 2.21 Å

Chemicals

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER / Diethylene glycol

ChemComp-GOL:
GLYCEROL / Glycerol

ChemComp-HOH:
WATER / Water

ChemComp-MG:
Unknown entry

Source
  • brevibacillus brevis nbrc 100599 (bacteria)
KeywordsBIOSYNTHETIC PROTEIN / Ketosynthase / polyketide synthase / Claisen condensation / thiolase fold / Dehydratase / Double hot dog fold

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