1. Synthesis of L-2,3-diaminopropionic acid, a siderophore and antibiotic precursor.
- Author
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Kobylarz MJ, Grigg JC, Takayama SJ, Rai DK, Heinrichs DE, and Murphy ME
- Subjects
- Bacterial Proteins biosynthesis, Bacterial Proteins chemistry, Bacterial Proteins genetics, Bacterial Proteins metabolism, Binding Sites, Catalytic Domain, Citrates biosynthesis, Citrates chemistry, Crystallography, X-Ray, Glutamic Acid analogs & derivatives, Glutamic Acid metabolism, Hydrolysis, Ketoglutaric Acids chemistry, Ketoglutaric Acids metabolism, Molecular Dynamics Simulation, NAD chemistry, NAD metabolism, Phosphoserine analogs & derivatives, Phosphoserine metabolism, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins genetics, Siderophores chemistry, Staphylococcus aureus enzymology, beta-Alanine biosynthesis, beta-Alanine chemistry, Anti-Bacterial Agents chemistry, Siderophores biosynthesis, Staphylococcus aureus metabolism, beta-Alanine analogs & derivatives
- 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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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