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Abstract：
Advanced techniques can accelerate the pace of natural product discovery from microbes, which has been lagging behind the drug discovery era. Therefore, the present review article discusses the various interdisciplinary and cutting-edge techniques to present a concrete strategy that enables the high-throughput screening of novel natural compounds (NCs) from known microbes. Recent bioinformatics methods revealed that the microbial genome contains a huge untapped reservoir of silent biosynthetic gene clusters (BGC). This article describes several methods to identify the microbial strains with hidden mines of silent BGCs. Moreover, antiSMASH 5.0 is a free, accurate, and highly reliable bioinformatics tool discussed in detail to identify silent BGCs in the microbial genome. Further, the latest microbial culture technique, HiTES (high-throughput elicitor screening), has been detailed for the expression of silent BGCs using 500-1000 different growth conditions at a time. Following the expression of silent BGCs, the latest mass spectrometry methods are highlighted to identify the NCs. The recently emerged LAESI-IMS (laser ablation electrospray ionization-imaging mass spectrometry) technique, which enables the rapid identification of novel NCs directly from microtiter plates, is presented in detail. Finally, various trending \'dereplication\' strategies are emphasized to increase the effectiveness of NC screening.
摘要：
先进的技术可以加快从微生物中发现天然产物的步伐，一直落后于药物发现时代。因此,本综述文章讨论了各种跨学科和尖端技术，以提出一种具体策略，该策略可以从已知微生物中高通量筛选新型天然化合物（NC）。最近的生物信息学方法表明，微生物基因组包含一个巨大的未开发的沉默生物合成基因簇（BGC）库。本文介绍了几种鉴定具有隐性BGC隐矿的微生物菌株的方法。此外，AntiSMASH5.0是免费的，准确,和高度可靠的生物信息学工具进行了详细讨论，以识别微生物基因组中的沉默BGC。Further,最新的微生物培养技术,HiTES（高通量诱导子筛选），已经详细描述了一次使用500-1000种不同生长条件的沉默BGC的表达。在沉默的BGC表达之后，强调了最新的质谱方法来识别NC。最近出现的LAESI-IMS（激光烧蚀电喷雾电离成像质谱）技术，这使得能够直接从微量滴定板快速鉴定新型NC，详细介绍了。最后,强调各种趋势“去复制”策略，以提高NC筛查的有效性。
