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Title: Siderophore Synthetase DesD Catalyzes N-to-C Condensation in Desferrioxamine Biosynthesis
Desferrioxamine siderophores are assembled by the nonribosomal-peptide-synthetase-independent-siderophore (NIS) synthetase enzyme DesD via ATP-dependent iterative condensation of three N1-hydroxy-N1-succinyl-cadaverine (HSC) units. Current knowledge of NIS enzymology and the desferrioxamine bio-synthetic pathway does not account for the existence of most known members of this natural product family which differ in substitution patterns of the N- and C-termini. The directionality of desferrioxamine biosyn-thetic assembly, N-to-C vs C-to-N, is a longstanding knowledge gap that is limiting further progress in un-derstanding the origins of natural products in this structural family. Here, we establish the directionality of desferrioxamine biosynthesis using a chemoenzymatic approach with stable isotope incorporation and di-meric substrates. We propose a mechanism where DesD catalyzes the N-to-C condensation of HSC units to establish a unifying biosynthetic paradigm for desferrioxamine natural products in Streptomyces.  more » « less
Award ID(s):
1654611
PAR ID:
10505308
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
American Chemical Society
Date Published:
Journal Name:
ACS Chemical Biology
Volume:
18
Issue:
6
ISSN:
1554-8929
Page Range / eLocation ID:
1266 to 1270
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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