Bartlett Christopher, Bansal Sonal, Burnett Alysha, Suits Michael D, Schaefer Jacob, Cegelski Lynette, Horsman Geoff P, Weadge Joel T
Department of Chemistry, Washington University , St. Louis, Missouri 63130, United States.
Department of Chemistry, Stanford University , Stanford, California 94305, United States.
Biochemistry. 2017 Nov 7;56(44):5870-5873. doi: 10.1021/acs.biochem.7b00814.
Naturally produced molecules possessing a C-P bond, such as phosphonates and phosphinates, remain vastly underexplored. Although success stories like fosfomycin have reinvigorated small molecule phosphonate discovery efforts, bioinformatic analyses predict an enormous unexplored biological reservoir of C-P bond-containing molecules, including those attached to complex macromolecules. However, high polarity, a lack of chromophores, and complex macromolecular association impede phosphonate discovery and characterization. Here we detect widespread transcriptional activation of phosphonate biosynthetic machinery across diverse bacterial phyla and describe the use of solid-state nuclear magnetic resonance to detect C-P bonds in whole cells of representative Gram-negative and Gram-positive bacterial species. These results suggest that phosphonate tailoring is more prevalent than previously recognized and set the stage for elucidating the fascinating chemistry and biology of these modifications.
天然产生的含有碳 - 磷（C-P）键的分子，如膦酸盐和次膦酸盐，仍未得到充分研究。尽管像磷霉素这样的成功案例重新激发了小分子膦酸盐的发现工作，但生物信息学分析预测，含C-P键分子的巨大生物库尚未被探索，包括那些与复杂大分子相连的分子。然而，高极性、缺乏发色团以及复杂的大分子缔合阻碍了膦酸盐的发现和表征。在这里，我们检测到不同细菌门类中膦酸盐生物合成机制的广泛转录激活，并描述了使用固态核磁共振来检测代表性革兰氏阴性和革兰氏阳性细菌物种全细胞中的C-P键。这些结果表明，膦酸盐修饰比以前认为的更为普遍，并为阐明这些修饰引人入胜的化学和生物学特性奠定了基础。
