Frontiers in Catalysis (Jun 2023)
Exploring the selectivity and engineering potential of an NRPS condensation domain involved in the biosynthesis of the thermophilic siderophore fuscachelin
- Y. T. Candace Ho,
- Y. T. Candace Ho,
- Y. T. Candace Ho,
- Y. T. Candace Ho,
- Thierry Izoré,
- Thierry Izoré,
- Joe A. Kaczmarski,
- Joe A. Kaczmarski,
- Edward Marschall,
- Edward Marschall,
- Edward Marschall,
- Minuri S. Ratnayake,
- Minuri S. Ratnayake,
- Minuri S. Ratnayake,
- Julien Tailhades,
- Julien Tailhades,
- Julien Tailhades,
- David L. Steer,
- David L. Steer,
- Ralf B. Schittenhelm,
- Ralf B. Schittenhelm,
- Manuela Tosin,
- Colin J. Jackson,
- Colin J. Jackson,
- Colin J. Jackson,
- Colin J. Jackson,
- Max J. Cryle,
- Max J. Cryle,
- Max J. Cryle
Affiliations
- Y. T. Candace Ho
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Y. T. Candace Ho
- EMBL Australia, Monash University, Clayton, VIC, Australia
- Y. T. Candace Ho
- ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT, Australia
- Y. T. Candace Ho
- Department of Chemistry, University of Warwick, Coventry, United Kingdom
- Thierry Izoré
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Thierry Izoré
- EMBL Australia, Monash University, Clayton, VIC, Australia
- Joe A. Kaczmarski
- ARC Centre of Excellence in Synthetic Biology, Australian National University, Canberra, ACT, Australia
- Joe A. Kaczmarski
- Research School of Biology, Australian National University, Acton, ACT, Australia
- Edward Marschall
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Edward Marschall
- EMBL Australia, Monash University, Clayton, VIC, Australia
- Edward Marschall
- ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT, Australia
- Minuri S. Ratnayake
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Minuri S. Ratnayake
- EMBL Australia, Monash University, Clayton, VIC, Australia
- Minuri S. Ratnayake
- ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT, Australia
- Julien Tailhades
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Julien Tailhades
- EMBL Australia, Monash University, Clayton, VIC, Australia
- Julien Tailhades
- ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT, Australia
- David L. Steer
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- David L. Steer
- Monash Proteomics and Metabolomics Facility, Monash University, Clayton, VIC, Australia
- Ralf B. Schittenhelm
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Ralf B. Schittenhelm
- Monash Proteomics and Metabolomics Facility, Monash University, Clayton, VIC, Australia
- Manuela Tosin
- Department of Chemistry, University of Warwick, Coventry, United Kingdom
- Colin J. Jackson
- ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT, Australia
- Colin J. Jackson
- ARC Centre of Excellence in Synthetic Biology, Australian National University, Canberra, ACT, Australia
- Colin J. Jackson
- Research School of Biology, Australian National University, Acton, ACT, Australia
- Colin J. Jackson
- Research School of Chemistry, Australian National University, Acton, ACT, Australia
- Max J. Cryle
- Department of Biochemistry and Molecular Biology, The Monash Biomedicine Discovery Institute Monash University, Clayton, VIC, Australia
- Max J. Cryle
- EMBL Australia, Monash University, Clayton, VIC, Australia
- Max J. Cryle
- ARC Centre of Excellence for Innovations in Peptide and Protein Science, Canberra, ACT, Australia
- DOI
- https://doi.org/10.3389/fctls.2023.1184959
- Journal volume & issue
-
Vol. 3
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.
Keywords
- nonribosomal peptide (NRP)
- biosynthesis
- condensation domain
- peptidyl carrier protein
- biocatalysis
- depsipeptide
