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: 3280697
• 负责人: STEVEN J GOULD
• 金额: $ 16.18万
• 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/3280697
• 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.

我们建议继续我们的抗生素生物合成的研究，并将