Abstract
Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products, nucleic acids, and as chemical modification in protein and peptides, phosphorous can form P–N (phosphoramidate), P–S (phosphorothioate), and P–C (e.g., phosphonate and phosphinate) linkages. While rare, these moieties play critical roles in many processes and in all forms of life. In this review we thoroughly categorize P–N, P–S, and P–C natural organophosphorus compounds. Information on biological source, biological activity, and biosynthesis is included, if known. This review also summarizes the role of phosphorylation on unusual amino acids in proteins (N- and S-phosphorylation) and reviews the natural phosphorothioate (P–S) and phosphoramidate (P–N) modifications of DNA and nucleotides with an emphasis on their role in the metabolism of the cell. We challenge the commonly held notion that nonphosphate organophosphorus functional groups are an oddity of biochemistry, with no central role in the metabolism of the cell. We postulate that the extent of utilization of some phosphorus groups by life, especially those containing P–N bonds, is likely severely underestimated and has been largely overlooked, mainly due to the technological limitations in their detection and analysis.
Highlights
All life on Earth relies on phosphorous-containing compounds in metabolism
There are two different types of lysine N-phosphorylation that were detected as post-translational modifications (PTMs) on proteins
The emerging view of N-phosphorylation of arginine, lysine and histidine as widespread post-translational modifications (PTMs) utilized by virtually all clades of life opens an interesting possibility for N-phosphorylation of other nitrogen-containing functional groups in proteins
Summary
All life on Earth relies on phosphorous-containing compounds in metabolism. Phosphate esters (C-O-P) in particular play a central, uniting role for all living organisms on Earth. The glycocyamine kinases (EC 2.7.3.1) from the annelid Hediste diversicolor was shown to be responsible for the synthesis of the N-phosphoguanidine (28), it is unclear if N-phosphoguanidine (28) is a true endogenous phosphagen of Hediste diversicolor or any other species [102] While it is theoretically possible for N-phosphoguanidine to be formed in vivo and for compound 28 to be an important metabolite in the cell its importance in the cellular metabolism remains to be proven. Recent identification of taurocyamine kinases in a large number of non-annelid species, including trematodes Paragonimus westermani, Schistosoma japonicum, Clonorchis sinensis [82,83,86,87,88,89] and, in two isolated cases in unicellular oomycetes [82,83,86,87,88,89], suggests that the evolutionary and phylogenetic scope of alternative substrate specificities of phosphagen kinases may be more widespread than previously thought [105]. Despite being identified in a multitude of species the function of AMPN is unknown
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