Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module

Li, Xiuyuan; Sevillano, Natalia; La Greca, Florencia; Deis, Lindsay; Liu, Yu -Chen; Deller, Marc C.; Mathews, Irimpan I.; Matsui, Tsutomu; Cane, David E.; Craik, Charles S.; Khosla, Chaitan

doi:10.1021/jacs.8b02100

Title: Structure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module

Journal Article · 15 May 2018 · Journal of the American Chemical Society

DOI: https://doi.org/10.1021/jacs.8b02100 · OSTI ID:1476142

Li, Xiuyuan ^[1]; Sevillano, Natalia ^[2]; La Greca, Florencia ^[2]; Deis, Lindsay ^[1];

^[1]; Deller, Marc C. ^[3];

^[4]; Matsui, Tsutomu ^[4];

^[5];

^[2];

^[1]

Stanford Univ., Stanford, CA (United States)
University of California San Francisco, San Francisco, CA (United States)
Stanford Univ., Stanford, CA (United States); SLAC National Accelerator Lab., Stanford Univ., Menlo Park, CA (United States)
SLAC National Accelerator Lab., Stanford Univ., Menlo Park, CA (United States)
Brown Univ., Providence, RI (United States)

Catalytic modules of assembly-line polyketide synthases (PKSs) have previously been observed in two very different conformations—an “extended” architecture and an “arch-shaped” architecture—although the catalytic relevance of neither has been directly established. By the use of a fully human naïve antigen-binding fragment (F_ab) library, a high-affinity antibody was identified that bound to the extended conformation of a PKS module, as verified by X-ray crystallography and tandem size-exclusion chromatography–small-angle X-ray scattering (SEC–SAXS). Kinetic analysis proved that this antibody-stabilized module conformation was fully competent for catalysis of intermodular polyketide chain translocation as well as intramodular polyketide chain elongation and functional group modification of a growing polyketide chain. Furthermore, the extended conformation of a PKS module is fully competent for all of its essential catalytic functions.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515; P41CA196276; GM022172; GM104659; GM087934

OSTI ID:: 1476142

Journal Information:: Journal of the American Chemical Society, Vol. 140, Issue 21; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 24 works

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