Open AccessStructure–Function Analysis of the Extended Conformation of a Polyketide Synthase Module
Author(s) -
Xiuyuan Li,
Natalia Sevillano,
Florencia La Greca,
L.N. Deis,
Yu Chen Liu,
Marc C. Deller,
I.I. Mathews,
Tsutomu Matsui,
David E. Cane,
Charles S. Craik,
Chaitan Khosla
Publication year - 2018
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.8b02100
Subject(s) - polyketide , chemistry , polyketide synthase , stereochemistry , catalysis , function (biology) , small angle x ray scattering , tandem , biosynthesis , crystallography , enzyme , biochemistry , scattering , biology , physics , materials science , composite material , evolutionary biology , optics
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. Thus, the extended conformation of a PKS module is fully competent for all of its essential catalytic functions.