Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: The structural organization of substrate loading in iterative polyketide synthases.

Authors: Herbst, Dominik A; Huitt-Roehl, Callie R; Jakob, Roman P; Kravetz, Jacob M; Storm, Philip A; Alley, Jamie R; Townsend, Craig A; Maier, Timm

Published In Nat Chem Biol, (2018 05)

Abstract: Polyketide synthases (PKSs) are microbial multienzymes for the biosynthesis of biologically potent secondary metabolites. Polyketide production is initiated by the loading of a starter unit onto an integral acyl carrier protein (ACP) and its subsequent transfer to the ketosynthase (KS). Initial substrate loading is achieved either by multidomain loading modules or by the integration of designated loading domains, such as starter unit acyltransferases (SAT), whose structural integration into PKS remains unresolved. A crystal structure of the loading/condensing region of the nonreducing PKS CTB1 demonstrates the ordered insertion of a pseudodimeric SAT into the condensing region, which is aided by the SAT-KS linker. Cryo-electron microscopy of the post-loading state trapped by mechanism-based crosslinking of ACP to KS reveals asymmetry across the CTB1 loading/-condensing region, in accord with preferential 1:2 binding stoichiometry. These results are critical for re-engineering the loading step in polyketide biosynthesis and support functional relevance of asymmetric conformations of PKSs.

PubMed ID: 29610486 Exiting the NIEHS site

MeSH Terms: Acyl Carrier Protein/chemistry*; Ascomycota/metabolism; Catalytic Domain; Cross-Linking Reagents/chemistry; Cryoelectron Microscopy; Crystallography, X-Ray; Escherichia coli/metabolism; Pantetheine/chemistry; Phosphorylation; Polyketide Synthases/chemistry*; Propionates/chemistry; Protein Conformation; Protein Domains; Protein Multimerization; Substrate Specificity

to Top