Exploring the selectivity and engineering potential of an NRPS condensation domain involved in the biosynthesis of the thermophilic siderophore fuscachelin

Y. T. Candace Ho; Thierry Izoré; Joe A. Kaczmarski; Edward Marschall; Minuri S. Ratnayake; Julien Tailhades; David L. Steer; Ralf B. Schittenhelm; Manuela Tosin; Colin J. Jackson; Max J. Cryle

doi:10.3389/fctls.2023.1184959

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Exploring the selectivity and engineering potential of an NRPS condensation domain involved in the biosynthesis of the thermophilic siderophore fuscachelin

Authors

Ho, Y. T. Candace^{1, 2, 3, 4}
Izoré, Thierry^{1, 2}
Kaczmarski, Joe A.^{5, 6}
Marschall, Edward^{1, 2, 3}
Ratnayake, Minuri S.^{1, 2, 3}
Tailhades, Julien^{1, 2, 3}
Steer, David L.^{1, 2}
Schittenhelm, Ralf B.^{1, 2}
Tosin, Manuela⁴
Jackson, Colin J.^{3, 5, 6, 6}
Cryle, Max J.^{1, 2, 3}

¹ The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC , (Australia)
² Monash University, Clayton, VIC , (Australia)
³ ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT , (Australia)
⁴ University of Warwick, Coventry , (United Kingdom)
⁵ Australian National University, Canberra, ACT , (Australia)
⁶ Australian National University, Acton, ACT , (Australia)

Type

Published Article

Journal

Frontiers in Catalysis

Publisher

Frontiers Media S.A.

Publication Date

Jun 16, 2023

Volume

3

Identifiers

DOI: 10.3389/fctls.2023.1184959

Source

Frontiers

Keywords

Disciplines

Catalysis
Original Research

License

Green

Abstract

In nonribosomal peptide synthesis, condensation (C) domains are key catalytic domains that most commonly link carrier protein bound substrates to form peptides or depsipeptides. While adenylation domains have been well characterized due to their role in the selection of monomers and hence as gate keepers in nonribosomal peptide biosynthesis, C-domains have been the subject of debate as they do not have apparent “A-domain like” side chain selectivity for their acceptor substrates. To probe the selectivity and specificity of C-domains, here we report our biochemical and structural characterization of the C3-domain from the biosynthesis of the siderophore fusachelin. Our results show that this C-domain is not broadly flexible for monomers bearing significantly alternated side chains or backbones, which suggests there can be a need to consider C-domain specificity for acceptor substrates when undertaking NRPS engineering.

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