Synthesis of L-2,3-Diaminopropionic Acid, a Siderophore and Antibiotic Precursor
Synthesis of L-2,3-Diaminopropionic Acid, a Siderophore and Antibiotic Precursor
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DOI：
10.1016/j.chembiol.2013.12.011
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发表时间：
2014-03-20
影响因子：
--
通讯作者：
Murphy, Michael E. P.
中科院分区：
文献类型：
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作者：
Kobylarz, Marek J.;Grigg, Jason C.;Murphy, Michael E. P.
L-2，3-二氨基丙酸（L-Dap）是一种氨基酸，是抗生素和葡萄球菌铁蛋白B（由金黄色葡萄球菌产生的铁载体）的前体。SbnA和Sbn B由葡萄球菌铁蛋白B生物合成基因簇编码，并与L-Dap生物合成有关。我们在这里证明，SbnA使用PLP和底物O-磷酸-L-丝氨酸和L-谷氨酸产生代谢产物N-（1-氨基-1-羧基-2-乙基）-谷氨酸（ACEGA）。SbnB显示使用NAD（+）氧化水解ACEGA以产生α-酮戊二酸和L-Dap。此外，我们还描述了SbnB与NADH和ACEGA以及NAD（+）和α-酮戊二酸的复合物的晶体结构，以揭示底物结合、氧化和水解所需的残基。SbnA和SbnB参与了S.金黄色葡萄球菌，其能够在缺乏活性三羧酸循环的情况下生物合成葡萄球菌铁蛋白B。
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 alpha-ketoglutarate and L-Dap. Also, we describe crystal structures of SbnB in complex with NADH and ACEGA as well as with NAD(+) and alpha-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.