Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access countless polyketide product structures. Using cryogenic electron microscopy to study DEBS module 1, we present a structural model describing this substrate-channeling phenomenon. Our 3.2- to 4.3-angstrom-resolution structures of the intact module reveal key domain-domain interfaces and highlight an unexpected module asymmetry. We also present the structure of a product-bound module that shines light on a recently described ""turnstile"" mechanism for transient gating of active sites along the assembly line.
        
Representative scheme of Thioesterase structure and an image from PDBsum server
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7M7E Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
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7M7EFold classification based on Structure-Structure alignment of Proteins - FSSP server