Letter abstract
Nature Chemical Biology 3, 652 - 656 (2007)
Published online: 19 August 2007 | doi:10.1038/nchembio.2007.23
A new family of ATP-dependent oligomerization-macrocyclization biocatalysts
Nadia Kadi1, Daniel Oves-Costales1, Francisco Barona-Gomez1,2 & Gregory L Challis1
Oligomerization and macrocyclization reactions are key steps in the biosynthesis of many bioactive natural products. Important macrocycles include the antibiotic daptomycin (1; ref. 1), the immunosuppressant FK-506 (2; ref. 2), the anthelmintic avermectin B1a (3; ref. 3) and the insecticide spinosyn A (4; ref. 4); important oligomeric macrocycles include the siderophores enterobactin (5; ref. 5) and desferrioxamine E (6; ref. 6). Biosynthetic oligomerization and macrocyclization reactions typically involve covalently tethered intermediates and are catalyzed by thioesterase domains of polyketide synthase and nonribosomal peptide synthetase multienzymes7. Here we report that the purified recombinant desferrioxamine siderophore synthetase DesD from Streptomyces coelicolor M145 catalyzes ATP-dependent trimerization-macrocyclization of a chemically synthesized 10-aminocarboxylic acid substrate via noncovalently bound intermediates. DesD is dissimilar to other known synthetase families but is similar to other enzymes known or proposed to be required for the biosynthesis of 
-aminocarboxylic acid–derived cyclodimeric siderophores8, 9. This suggests that DesD is the first biochemically characterized member of a new family of oligomerizing and macrocyclizing synthetases.
- Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
- Present address: Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, C.P. 62250, México.
Correspondence to: Gregory L Challis1 e-mail: g.l.challis@warwick.ac.uk
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