Trivella Daniela B B, de Felicio Rafael
Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Sao Paulo, Brazil.
mSystems. 2018 Mar 27;3(2). doi: 10.1128/mSystems.00160-17. eCollection 2018 Mar-Apr.
Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Further progress in compound detection, such as the development of the tandem mass spectrometry (MS/MS) molecular networking approach, has contributed to the discovery of novel bacterial natural products. The latter can be applied directly to bacterial crude extracts for identifying and dereplicating known compounds, therefore assisting the prioritization of extracts containing novel natural products, for example. In our opinion, these three approaches-genome mining, silent pathway induction, and MS-based molecular networking-compose the tripod for modern bacterial natural product discovery and will be discussed in this perspective.
天然产物是药物发现中化合物最丰富的来源。特别是，由于基因组测序和挖掘技术的进步，以及在实验室培养条件下通过生物合成途径操纵唤醒沉默（隐秘）基因簇的潜力，细菌次级代谢产物备受关注。化合物检测方面的进一步进展，如串联质谱（MS/MS）分子网络方法的发展，有助于发现新型细菌天然产物。例如，后者可直接应用于细菌粗提物，用于鉴定已知化合物并去除重复，从而有助于对含有新型天然产物的提取物进行优先级排序。我们认为，这三种方法——基因组挖掘、沉默途径诱导和基于质谱的分子网络——构成了现代细菌天然产物发现的三脚架，并将从这个角度进行讨论。
