用糖脂基质修改细菌细胞壁
Phillip J Calabretta1, Heather L Hodges, Matthew B Kraft
1Department of Chemistry , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
Journal of the American Chemical Society
|May 14, 2019
概括
研究人员开发了一种新的策略,使用合成脂质链接的甘氨酸来探测细菌细胞壁结构. 这种方法克服了传统代谢结合的局限性,使复杂的甘氨酸生物合成能够进行详细的分析和操纵.
科学领域:
- 微生物学
- 葡萄糖生物学
- 合成生物学
背景情况:
- 甘氨酸在生物过程中至关重要,但研究它们的细胞结构的方法有限.
- 非天然糖的代谢结合是一种常见的技术,但它面临着复杂的细菌途径和反抗性结构的挑战.
- 现有的方法通常集中在核酸糖上,在了解其他生物合成中间体方面留下了空白.
研究的目的:
- 开发一种新的策略,用于探测使用代谢结合的难以研究的细菌糖结构.
- 通过准与脂质结合的甘氨酸中间体来补充现有的聚焦于核酸糖的方法.
- 研究合成甘油脂作为化学补充和细胞壁分析的生物合成中间体的潜力.
主要方法:
- 合成的阿拉比诺酸脂作为非天然的糖脂供体.
- 在Corynebacterium glutamicum和Mycobacterium smegmatis模型中测试合成供体.
- 使用C. glutamicum突变缺乏阿拉比南用于化学补充实验.
- 使用同位素标记的糖基质通过NMR进行细胞壁表征.
- 评估通过阿拉比诺酸转移酶对合成捐赠体的处理及其对细胞包膜恢复的影响.
主要成果:
- 在C. glutamicum突变体中,合成的非天然甘油脂成功地作为生物合成中间体,恢复细胞壁阿拉比南.
- 添加基于合成脂质的探针允许使用NMR进行全面的细胞壁表征.
- 所有已知的5种阿拉比诺转移酶都处理了外源性脂质结合糖的供体,从而使细胞外完全恢复.
- 这种基于脂质的探针可以拯救用细胞壁生物合成抑制剂治疗的野生细胞.
结论:
- 自然脂质结合甘氨酸的替代物可以有效地干预细胞甘氨酸生物合成途径.
- 合成脂质结合甘氨酸的生物合成结合是检测细菌中的甘氨酸结构和功能的有效策略.
- 这种方法为研究复杂的糖结构提供了有价值的替代方法.
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