期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 13, 页码 5226-5231出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1012813108
关键词
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资金
- National Institutes of Health [T32GM067550, GM085283]
- Los Angeles Chapter of the Achievement Rewards for College Scientists (ARCS) Foundation
- National Oceanic and Atmospheric Administration (NOAA) [NA08OAR4170669]
- California Sea Grant College through NOAA's National Sea Grant College [SG-100-TECH-N]
- US Department of Commerce
Sessile marine organisms are prolific sources of biologically active natural products. However, these compounds are often found in highly variable amounts, with the abiotic and biotic factors governing their production remaining poorly understood. We present an approach that permits monitoring of in vivo natural product production and turnover using mass spectrometry and stable isotope (N-15) feeding with small cultures of various marine strains of the natural product-rich cyanobacterial genus Lyngbya. This temporal comparison of the amount of in vivo N-15 labeling of nitrogen-containing metabolites represents a direct way to discover and evaluate factors influencing natural product biosynthesis, as well as the timing of specific steps in metabolite assembly, and is a strong complement to more traditional in vitro studies. Relative quantification of N-15 labeling allowed the concurrent measurement of turnover rates of multiple natural products from small amounts of biomass. This technique also afforded the production of the neurotoxic jamaicamides to be more carefully studied, including an assessment of how jamaicamide turnover compares with filament growth rate and primary metabolism and provided new insights into the biosynthetic timing of jamaicamide A bromination. This approach should be valuable in determining how environmental factors affect secondary metabolite production, ultimately yielding insight into the energetic balance among growth, primary production, and secondary metabolism, and thus aid in the development of methods to improve compound yields for biomedical or biotechnological applications.
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