Structures of a non-ribosomal peptide synthetase condensation domain suggest the basis of substrate selectivity

Thierry Izoré (), Y. T. Candace Ho, Joe A. Kaczmarski, Athina Gavriilidou, Ka Ho Chow, David L. Steer, Robert J. A. Goode, Ralf B. Schittenhelm, Julien Tailhades, Manuela Tosin, Gregory L. Challis, Elizabeth H. Krenske, Nadine Ziemert, Colin J. Jackson and Max J. Cryle ()
Additional contact information
Thierry Izoré: Monash University
Y. T. Candace Ho: Monash University
Joe A. Kaczmarski: The Australian National University
Athina Gavriilidou: Interfaculty Institute of Microbiology and Infection Medicine Tübingen, Microbiology/Biotechnology, University of Tübingen
Ka Ho Chow: The University of Queensland
David L. Steer: Monash University
Robert J. A. Goode: Monash University
Ralf B. Schittenhelm: Monash University
Julien Tailhades: Monash University
Manuela Tosin: University of Warwick
Gregory L. Challis: Monash University
Elizabeth H. Krenske: The University of Queensland
Nadine Ziemert: German Centre for Infection Research (DZIF), Partnersite Tübingen
Colin J. Jackson: ARC Centre of Excellence for Innovations in Peptide and Protein Science
Max J. Cryle: Monash University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Non-ribosomal peptide synthetases are important enzymes for the assembly of complex peptide natural products. Within these multi-modular assembly lines, condensation domains perform the central function of chain assembly, typically by forming a peptide bond between two peptidyl carrier protein (PCP)-bound substrates. In this work, we report structural snapshots of a condensation domain in complex with an aminoacyl-PCP acceptor substrate. These structures allow the identification of a mechanism that controls access of acceptor substrates to the active site in condensation domains. The structures of this complex also allow us to demonstrate that condensation domain active sites do not contain a distinct pocket to select the side chain of the acceptor substrate during peptide assembly but that residues within the active site motif can instead serve to tune the selectivity of these central biosynthetic domains.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22623-0

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DOI: 10.1038/s41467-021-22623-0

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