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Publication Abstract from PubMed

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.

Mapping the catalytic conformations of an assembly-line polyketide synthase module.,Cogan DP, Zhang K, Li X, Li S, Pintilie GD, Roh SH, Craik CS, Chiu W, Khosla C Science. 2021 Nov 5;374(6568):729-734. doi: 10.1126/science.abi8358. Epub 2021 , Nov 4. PMID:34735239^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.