ACS Chem Biol. 2013 May 17;8(5):908-13. doi: 10.1021/cb400102t. Epub 2013 Mar 13.
Naturally occurring phosphonates such as phosphinothricin (Glufosinate, a commercially used herbicide) and fosfomycin (Monurol, a clinically used antibiotic) have proved to be potent and useful biocides. Yet this class of natural products is still an under explored family of secondary metabolites. Discovery of the biosynthetic pathways responsible for the production of these compounds has been simplified by using gene based screening approaches, but detection and identification of the natural products the genes produce have been hampered by a lack of high-throughput methods for screening potential producers under various culture conditions. Here, we present an efficient mass-spectrometric method for the selective detection of natural products containing phosphonate and phosphinate functional groups. We have used this method to identify a new phosphonate metabolite, phosacetamycin, whose structure, biological activity, and biosynthetic gene cluster are reported.
天然存在的膦酸盐，如磷丝氨酸（草铵膦，一种商业上使用的除草剂）和磷霉素（Monurol，一种临床上使用的抗生素）已被证明是有效的和有用的杀菌剂。然而，这类天然产物仍然是一个未被充分探索的次级代谢产物家族。通过使用基于基因的筛选方法，已经简化了负责这些化合物产生的生物合成途径的发现，但由于缺乏用于在各种培养条件下筛选潜在生产者的高通量方法，对基因产生的天然产物的检测和鉴定受到了阻碍。在这里，我们提出了一种有效的质谱检测方法，用于选择性检测含有膦酸和膦酸盐官能团的天然产物。我们已经使用该方法鉴定了一种新的膦酸盐代谢物，phosacetamycin，其结构、生物活性和生物合成基因簇已被报道。
