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The modules of trans ‐acyltransferase assembly lines redefined with a central acyl carrier protein
Author(s) -
Vander Wood Drew A.,
KeatingeClay Adrian T.
Publication year - 2018
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25493
Subject(s) - polyketide synthase , acyl carrier protein , nonribosomal peptide , acyltransferase , polyketide , acyltransferases , assembly line , enzyme , biology , function (biology) , stereochemistry , moiety , computational biology , chemistry , biochemistry , microbiology and biotechnology , biosynthesis , mechanical engineering , engineering
Abstract Here, the term “module” is redefined for trans ‐acyltransferase ( trans ‐AT) assembly lines to agree with how its domains cooperate and evolutionarily co‐migrate. The key domain in both the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) modules of assembly lines is the acyl carrier protein (ACP). ACPs not only relay growing acyl chains through the assembly line but also collaborate with enzymes in modules, both in cis and in trans , to add a specific chemical moiety. A ketosynthase (KS) downstream of ACP often plays the role of gatekeeper, ensuring that only a single intermediate generated by the enzymes of a module is passed downstream. Bioinformatic analysis of 526 ACPs from 33 characterized trans ‐AT assembly lines reveals ACPs from the same module type generally clade together, reflective of the co‐evolution of these domains with their cognate enzymes. While KSs downstream of ACPs from the same module type generally also clade together, KSs upstream of ACPs do not—in disagreement with the traditional definition of a module. Beyond nomenclature, the presented analysis impacts our understanding of module function, the evolution of assembly lines, pathway prediction, and assembly line engineering.