Bluhm Martin E, Hay Benjamin P, Kim Sanggoo S, Dertz Emily A, Raymond Kenneth N
W. R. Wiley Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352-9904, USA.
Inorg Chem. 2002 Oct 21;41(21):5475-8. doi: 10.1021/ic025531y.
Because the hydrolysis of ferric ion makes it very insoluble in aerobic, near neutral pH environments, most species of bacteria produce siderophores to acquire iron, an essential nutrient. The chirality of the ferric siderophore complex plays an important role in cell recognition, uptake, and utilization. Corynebactin, isolated from Gram-positive bacteria, is structurally similar to enterobactin, a well-known siderophore first isolated from Gram-negative bacteria, but contains L-threonine instead of L-serine in the trilactone backbone. Corynebactin also contains a glycine spacer unit in each of the chelating arms. A hybrid analogue (serine-corynebactin) has been prepared which has the trilactone ring of enterobactin and the glycine spacer of corynebactin. The chirality and relative conformational stability of the three ferric complexes of enterobactin, corynebactin, and the hybrid have been investigated by molecular modeling (including MM3 and pBP86/DN density functional theory calculations) and circular dichroism spectra. While enterobactin forms a Delta-ferric complex, corynebactin is Lambda. The hybrid serine-corynebactin forms a nearly racemic mixture, with the Lambda-conformer in slight excess. Each ferric complex has four possible isomers depending on the metal chirality and the conformation of the trilactone ring. For corynebactin, the energy difference between the two possible Lambda conformations is 2.3 kcal/mol. In contrast, only 1.5 kcal/mol separates the inverted Lambda- and normal Delta-configuration for serine-corynebactin. The small energy difference of the two lowest energy configurations is the likely cause for the racemic mixture found in the CD spectra. Both the addition of a glycine spacer and methylation of the trilactone ring (serine to threonine) favor the Lambda-conformation. These structural changes suffice to change the chirality from all Delta (enterobactin) to all Lambda (corynebactin). The single change (glycine spacer) of the hybrid ferric serine-corynebactin gives a mixture of Delta and Lambda, with the Lambda in slight excess.
由于铁离子的水解使其在有氧、接近中性pH值的环境中极难溶解，大多数细菌种类会产生铁载体来获取铁这一必需营养素。铁载体-铁复合物的手性在细胞识别、摄取和利用中起着重要作用。从革兰氏阳性菌中分离出的棒状杆菌素，其结构与最早从革兰氏阴性菌中分离出的著名铁载体肠杆菌素相似，但在三内酯主链中含有L-苏氨酸而非L-丝氨酸。棒状杆菌素在每个螯合臂中还含有一个甘氨酸间隔单元。已制备出一种杂合类似物（丝氨酸-棒状杆菌素），它具有肠杆菌素的三内酯环和棒状杆菌素的甘氨酸间隔单元。通过分子建模（包括MM3和pBP86/DN密度泛函理论计算）和圆二色光谱研究了肠杆菌素、棒状杆菌素及其杂合物的三种铁复合物的手性和相对构象稳定性。肠杆菌素形成δ-铁复合物，而棒状杆菌素是λ-型。杂合丝氨酸-棒状杆菌素形成近乎外消旋的混合物，其中λ-构象体略占优势。根据金属手性和三内酯环的构象，每种铁复合物有四种可能的异构体。对于棒状杆菌素，两种可能的λ构象之间的能量差为2.3千卡/摩尔。相比之下，丝氨酸-棒状杆菌素的反向λ构型和正常δ构型之间的能量差仅为1.5千卡/摩尔。两种最低能量构型之间的小能量差可能是圆二色光谱中发现外消旋混合物的原因。甘氨酸间隔单元的添加和三内酯环的甲基化（丝氨酸变为苏氨酸）都有利于λ-构象。这些结构变化足以将手性从全δ型（肠杆菌素）变为全λ型（棒状杆菌素）。杂合铁丝氨酸-棒状杆菌素的单一变化（甘氨酸间隔单元）产生了δ型和λ型的混合物，其中λ型略占优势。
