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A new family of ATP-dependent oligomerization-macrocyclization biocatalysts
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Kadi, Nadia, Oves-Costales, Daniel, Barona-Gomez, Francisco and Challis, Gregory L. (2007) A new family of ATP-dependent oligomerization-macrocyclization biocatalysts. Nature, Vol.3 (No.10). pp. 652-656. doi:10.1038/nchembio.2007.23 ISSN 0028-0836.
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Official URL: http://dx.doi.org/10.1038/nchembio.2007.23
Abstract
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 multienzymes(7). 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 omega- aminocarboxylic acid - derived cyclodimeric siderophores(8,9). This suggests that DesD is the first biochemically characterized member of a new family of oligomerizing and macrocyclizing synthetases.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Library of Congress Subject Headings (LCSH): | Macrocyclic compounds, Ring formation (Chemistry), Oligomers, Adenosine triphosphate, Biosynthesis, Enzymes | ||||
| Journal or Publication Title: | Nature | ||||
| Publisher: | Nature Publishing | ||||
| ISSN: | 0028-0836 | ||||
| Official Date: | October 2007 | ||||
| Dates: |
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| Volume: | Vol.3 | ||||
| Number: | No.10 | ||||
| Number of Pages: | 5 | ||||
| Page Range: | pp. 652-656 | ||||
| DOI: | 10.1038/nchembio.2007.23 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) | ||||
| Grant number: | BBS/B/14450 (BBSRC), EGH16081 (BBSRC) | ||||
| Version or Related Resource: | Kadi, N., et al. (2009). Erratum : a new family of ATP-dependent oligomerization-macrocyclization biocatalysts. Nature Chemical Biology, 5(4), pp. 266-266. | ||||
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