Synthesis of L-2,3-Diaminopropionic Acid, a Siderophore and Antibiotic Precursor

• The product of SbnA is N-(1-amino-1-carboxyl-2-ethyl)-glutamic acid (ACEGA)
• Hydrolysis of ACEGA by SbnB yields L-2,3-diaminopropionate and α-ketoglutarate
• The substrates for SbnA are L-glutamate and O-phospho-L-serine
• SbnA and SbnB contribute to the iron-sparing response of S. aureus

SummaryL-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.

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