BIOSYNTHETIC STUDIES USING 15N 13C CNMR SPECTROSCOPY

使用 15N 13C CNMR 光谱进行生物合成研究

• 批准号: 3280696
• 负责人: STEVEN J GOULD
• 金额: $ 14.3万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3280696
• 关键词: Streptomyces; aminoacid metabolism; aminoglycoside antibiotics; antibiotics; arginine; biotransformation; chemical structure function; chloramphenicol; drug design /synthesis /production; glucose; hydroxyaminoacid; mass spectrometry; microorganism growth; microorganism metabolism; nuclear magnetic resonance spectroscopy; stereochemistry

We propose to continue our studies of antibiotic biosynthesis, and will focus on the secondary metabolism of amino acids and of glucose. With the former our emphasis will be on the generation of Beta-hydroxy-Alpha-amino acids and of Beta-amino acids as biosynthetic intermediates. This work will include further experiments on streptothricin F, blasticidin, negamycin and 3-epideoxynegamycin, and will be expanded to include the biogenetically relevant metabolites elastatinal, AT-125, and chloramphenicol in order to test our hypotheses on the formation and utilization of Beta-hydroxy amino acids. We will primarily use the stable isotopes 13C, 2H, 15N, and 18O and they will be detected by NMR spectroscopic techniques. A number of labeled compounds that will be synthesized will be used in more than one of these projects. Analysis of the isotope labeling patterns will again use our 15N/13C NMR spin coupling technique, will explore the utility of our new 1H/2H COSY technique for editing complex 2H NMR spectra, and will explore the utility of 3H NMR and of high resolution FAB mass spectrometry for locating isotope labels in complex metabolites. Our investigations will increase our understanding of which chemical reactions are available in Nature and how they can be linred to produce complex structures. They may also provide the opportunity to produce new analogs, also with antibiotic activity, by redirecting the microorganisms' biosynthetic apparatus to use modified precursors.

我们建议继续我们对抗生素生物合成的研究，并将 关注氨基酸和葡萄糖的次生代谢。与 以前我们的重点是生成β-羟基-α-氨基 酸和作为生物合成中间体的β-氨基酸。这部作品 将包括对链霉菌素F、杀菌素、 负霉素和3-表氧基负霉素，并将扩大到包括 生物遗传相关的代谢物弹性蛋白、AT-125和 为了验证我们关于氯霉素形成和形成的假设 β-羟基氨基酸的利用。我们将主要使用马厩 同位素13C、2H、15N和18O将通过核磁共振进行检测 光谱技术。一些标记的化合物将被 合成的将用于不止一个这样的项目。 对同位素标记模式的分析将再次使用我们的15N/13C核磁共振 自旋耦合技术，将探索我们新的1H/2H COSY的用途 编辑复杂的2H核磁共振谱的技术，并将探索该实用程序 ~3H核磁共振和高分辨FAB质谱学定位同位素 复杂代谢物中的标记。 我们的调查将增加我们对哪种化学物质 反应在《自然》中是可用的，以及它们如何被线性地产生 复杂的结构。它们还可能提供生产新产品的机会 类似物，也具有抗生素活性，通过改变微生物的 使用修饰前体物的生物合成装置。