Department of Microbiology, The Ohio State University, Columbus OH 43210, USA; Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus OH 43210, USA; Infectious Diseases Institute, The Ohio State University, Columbus OH 43210, USA.
Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois, Urbana, IL 61801, USA; Carl Woese Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, USA.
Curr Opin Chem Biol. 2022 Dec;71:102214. doi: 10.1016/j.cbpa.2022.102214. Epub 2022 Oct 3.
The phosphonate class of natural products have received significant interests in the post-genomic era due to the relative ease with which their biosynthetic genes may be identified and the resultant final products be characterized. Recent large-scale studies of the elucidation and distributions of phosphonate pathways have provided a robust landscape for deciphering the underlying biosynthetic logic. A recurrent theme in phosphonate biosynthetic pathways is the interweaving of enzymatic reactions across different routes, which enables diversification to elaborate chemically novel scaffolds. Here, we provide a few vignettes of how Nature has utilized both convergent and divergent biosynthetic strategies to compile pathways for production of novel phosphonates. These examples illustrate how common intermediates may either be generated or intercepted to diversify chemical scaffolds and provides a starting point for both biotechnological and synthetic biological applications towards new phosphonates by similar combinatorial approaches.
在基因组后时代，由于相对容易识别其生物合成基因，并且可以对最终产物进行特征分析，因此磷酸酯类天然产物受到了广泛关注。最近对磷酸酯途径的阐明和分布进行的大规模研究为破译潜在的生物合成逻辑提供了一个强有力的研究基础。磷酸酯生物合成途径的一个反复出现的主题是不同途径之间酶反应的交织，这使得多样化能够精心设计具有化学新颖性的支架。在这里，我们提供了一些示例来说明自然界如何利用趋同和发散的生物合成策略来编译生产新型磷酸酯的途径。这些例子说明了常见的中间体如何产生或被拦截来多样化化学支架，并为通过类似组合方法开发新型磷酸酯的生物技术和合成生物学应用提供了起点。
