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Synthesis of L-2,3-Diaminopropionic Acid, a Siderophore and Antibiotic Precursor
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2014-01-30 , DOI: 10.1016/j.chembiol.2013.12.011
Marek J. Kobylarz , Jason C. Grigg , Shin-ichi J. Takayama , Dushyant K. Rai , David E. Heinrichs , Michael E.P. Murphy

L-2,3-diaminopropionic acid (L-Dap) is an amino acid that is a precursor of antibiotics and staphyloferrin B a siderophore produced byStaphylococcus 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 substratesO-phospho-L-serine and L-glutamate to produce a metaboliteN-(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 ofS. aureusthat enables staphyloferrin B biosynthesis in the absence of an active tricarboxylic acid cycle.

中文翻译:

L-2,3-二氨基丙酸,铁载体和抗生素前体的合成

L-2,3-二氨基丙酸(L-Dap)是一种氨基酸,是抗生素的前体,而金黄色葡萄球菌B是一种由金黄色葡萄球菌产生的铁载体。SbnA和SbnB由葡萄铁蛋白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-谷氨酸来生产代谢产物N-(1-氨基-1-羧基-2-乙基)-谷氨酸(ACEGA)。已显示SbnB使用NAD +氧化水解ACEGA,生成α-酮戊二酸酯和L-Dap。此外,我们描述了与NADH和ACEGA以及与NAD +和α-酮戊二酸酯复合的SbnB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有助于S的铁节约反应。
更新日期:2017-01-31
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