Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
J Ind Microbiol Biotechnol. 2019 Mar;46(3-4):301-311. doi: 10.1007/s10295-019-02136-y. Epub 2019 Jan 25.
Bacterial metabolism is comprised of primary metabolites, the intracellular molecules of life that enable growth and proliferation, and secondary metabolites, predominantly extracellular molecules that facilitate a microbe's interaction with its environment. While our knowledge of primary metabolism and its web of interconnected intermediates is quantitative and holistic, significant knowledge gaps remain in our understanding of the secondary metabolomes of bacteria. In this Perspective, I discuss the main challenges involved in obtaining a global, comprehensive picture of bacterial secondary metabolomes, specifically in biosynthetically "gifted" microbes. Recent methodological advances that can meet these challenges will be reviewed. Applications of these methods combined with ongoing innovations will enable a detailed picture of global secondary metabolomes, which will in turn shed light onto the biology, chemistry, and enzymology underlying natural products and simultaneously aid drug discovery.
细菌代谢由初级代谢物和次级代谢物组成，前者是生命的细胞内分子，使细菌得以生长和增殖；后者主要是细胞外分子，有助于微生物与其环境相互作用。尽管我们对初级代谢及其相互关联的中间体网络有了定量和全面的了解，但对细菌次级代谢组的理解仍存在重大知识空白。在本文观点中，我讨论了获得细菌次级代谢组全面综合图谱所面临的主要挑战，特别是在生物合成上“有天赋”的微生物中。将综述可应对这些挑战的最新方法学进展。这些方法的应用与持续的创新相结合，将能够描绘出全球次级代谢组的详细图谱，这反过来又将揭示天然产物的生物学、化学和酶学基础，并同时有助于药物发现。
