Condensation domains: programming logic in nonribosomal peptide synthesis
🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 604 papers from lmmol's literature graph. Citations link to their source on PubMed.
| Protein | Papers |
|---|---|
| N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase | 20 |
| Nonribosomal peptide synthetase gliP | 20 |
| N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase | 16 |
| Enterobactin synthase component F | 16 |
| D-lysergyl-peptide-synthetase subunit 1 | 16 |
| D-lysergyl-peptide-synthetase subunit 2 | 16 |
| D-lysergyl-peptide-synthetase subunit 1 | 15 |
| D-lysergyl-peptide-synthetase subunit 1 | 15 |
Condensation (C) domains in nonribosomal peptide synthetases coordinate both chemistry and topology: they define how activated intermediates are passed forward and thus govern final peptide architecture [1][2]. Contemporary NRPS work has moved beyond cataloging modules toward mechanism-level questions on substrate channeling, communication motifs, and pathway-level branch points [3][4]. This makes C domains a high-value read through for drug-like natural product biology, especially where biosynthetic logic predicts bioactivity shifts before chemistry is finished [5][6].
1. What changed in the recent literature
The strongest papers increasingly couple structural snapshots with genetic perturbations, showing that condensation decisions are context-coded across whole modules and accessory proteins [7][8][9]. In this framework, “a C domain alone” is no longer a complete statement: pathway organization, docking interfaces, and cofactor timing carry comparable explanatory weight [10][11][12].
2. Practical reading priorities
For this family on lmmol, prioritize reviews and papers that compare homologous C-domain architectures with distinct product classes and then trace that to altered host interactions [3][6]. Especially in actinomycetes and fungal systems, C-domain studies that document partner selection and peptide diversification are the most transferable for synthesis, resistance, and translational design discussions [7][5][13].
3. Practical orientation for lmmol
Use topic ranking to favor studies where condensation-domain biology is experimentally linked to ecological or therapeutic phenotype, not only static domain annotation [9][3]. That is where lmmol's citation graph has most discriminative signal for “what is new” in secondary metabolism [2][6].
- N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase
- Nonribosomal peptide synthetase gliP
- Enterobactin synthase component F
- D-lysergyl-peptide-synthetase subunit 1
- D-lysergyl-peptide-synthetase subunit 2
- Lovastatin nonaketide synthase, polyketide synthase component
- Mycosubtilin synthetase of Bacillus subtilis ATCC6633
- Nonribosomal peptide synthetase sidC
References
- Conti E., Stachelhaus T., Marahiel M.A., Brick P. Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S. EMBO J 1997. PubMed 567×
- De Voss J.J., Rutter K., Schroeder B.G., Su H. et al. The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages. Proc. Natl. Acad. Sci. U.S.A 2000. PubMed 450×
- Gross H., Loper J.E. Genomics of secondary metabolite production by Pseudomonas spp. Nat. Prod. Rep 2009. PubMed 400×
- Ma S.M., Li J.W., Choi J.W., Zhou H. et al. Complete reconstitution of a highly reducing iterative polyketide synthase. Science 2009. PubMed 268×
- May J.J., Wendrich T.M., Marahiel M.A. The dhb operon of Bacillus subtilis encodes the biosynthetic template for the catecholic siderophore 2,3-dihydroxybenzoate-glycine-threonine trimeric ester bacillibactin. J. Biol. Chem 2001. PubMed 270×
- Drake E.J., Miller B.R., Shi C., Tarrasch J.T. et al. Structures of two distinct conformations of holo-non-ribosomal peptide synthetases. Nature 2016. PubMed 196×
- Oide S., Moeder W., Krasnoff S., Gibson D. et al. NPS6, encoding a nonribosomal peptide synthetase involved in siderophore-mediated iron metabolism, is a conserved virulence determinant of plant pathogenic ascomycetes. Plant Cell 2006. PubMed 257×
- Kraetzschmar J., Krause M., Marahiel M.A. Gramicidin S biosynthesis operon containing the structural genes grsA and grsB has an open reading frame encoding a protein homologous to fatty acid thioesterases. J. Bacteriol 1989. PubMed 201×
- Boehnert H.U., Fudal I., Dioh W., Tharreau D. et al. A putative polyketide synthase/peptide synthetase from Magnaporthe grisea signals pathogen attack to resistant rice. Plant Cell 2004. PubMed 232×
- Bruner S.D., Weber T., Kohli R.M., Schwarzer D. et al. Structural basis for the cyclization of the lipopeptide antibiotic surfactin by the thioesterase domain SrfTE. Structure 2002. PubMed 187×
- Duitman E.H., Hamoen L.W., Rembold M., Venema G. et al. The mycosubtilin synthetase of Bacillus subtilis ATCC6633: a multifunctional hybrid between a peptide synthetase, an amino transferase, and a fatty acid synthase. Proc. Natl. Acad. Sci. U.S.A 1999. PubMed 206×
- Mootz H.D., Marahiel M.A. The tyrocidine biosynthesis operon of Bacillus brevis: complete nucleotide sequence and biochemical characterization of functional internal adenylation domains. J. Bacteriol 1997. PubMed 233×
- Turgay K., Krause M., Marahiel M.A. Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate-forming enzymes. Mol. Microbiol 1992. PubMed 205×