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Chem Biol. 2014 Mar 20;21(3):379-88. doi: 10.1016/j.chembiol.2013.12.011. Epub 2014 Jan 30.

Synthesis of L-2,3-diaminopropionic acid, a siderophore and antibiotic precursor.

Author information

1
Department of Microbiology and Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
2
Department of Microbiology and Immunology, The Centre for Human Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.
3
Department of Microbiology and Immunology, Life Sciences Institute, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: michael.murphy@ubc.ca.

Abstract

L-2,3-diaminopropionic acid (L-Dap) is an amino acid that is a precursor of antibiotics and staphyloferrin B a siderophore produced by Staphylococcus aureus. SbnA and SbnB are encoded by the staphyloferrin B biosynthetic gene cluster and are implicated in L-Dap biosynthesis. We demonstrate here that SbnA uses PLP and substrates O-phospho-L-serine and L-glutamate to produce a metabolite N-(1-amino-1-carboxyl-2-ethyl)-glutamic acid (ACEGA). SbnB is shown to use NAD(+) to oxidatively hydrolyze ACEGA to yield α-ketoglutarate and L-Dap. Also, we describe crystal structures of SbnB in complex with NADH and ACEGA as well as with NAD(+) and α-ketoglutarate to reveal the residues required for substrate binding, oxidation, and hydrolysis. SbnA and SbnB contribute to the iron sparing response of S. aureus that enables staphyloferrin B biosynthesis in the absence of an active tricarboxylic acid cycle.

PMID:
24485762
DOI:
10.1016/j.chembiol.2013.12.011
[Indexed for MEDLINE]
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