Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

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.

Phosphonates: Their Natural Occurrence and Physiological Role

“…It is not surprising if considering that ciliatine is a formal analog of common component of lipids-phosphoethanolamine (compound 4). Most of the studies on natural occurrence of ciliatine and its lipids had been published in 1960-1990 and are comprehensively reviewed [2][3][4][5]. Only single paper was published after this period.…”

“…This is not the case in science currently because of their involvement in the global phosphorus cycle and in oceanic methane production. Some aspects of their occurrence, environmental role, biochemistry, and biological functions have been reviewed [2][3][4][5]. This chapter will concentrate on discussion of chemical diversity of the naturally occurring phosphonates and on the indication of open problems, which have not yet been solved.…”

Trivalent Phosphorus and Phosphines as Components of Biochemistry in Anoxic Environments

“…However, almost all of life's use of phosphorus is as phosphorus in the +5 oxidation state, and almost all of the phosphorus-containing compounds that are made by life are phosphates. Other phosphorus compounds that link phosphorus with five covalent bonds (hereafter pentavalent phosphorus 1 ) to nitrogen, sulfur, or carbon atoms are known in some natural products, but are rare: only *130 compounds are known, which contain phosphorus atoms that are not in a phosphate group (see Petkowski et al (2019a) for descriptions of the databases used to draw these conclusions; for the recent review on the utilization of the rare organophosphorus funtional groups by life on Earth, see Petkowski et al, 2019b). The structural similarity between these compounds is clear (Table 1).…”

Pseudoceratonic Acid and Moloka’iamine Derivatives from the Red Sea Verongiid Sponge Pseudoceratina arabica

“…Hydrazine derivatives and other dinitrogen-containing features are commonly found in natural compounds of terrestrial, microbial, and marine origin [23,24]. Similarly, derivatives of phosphoramidic acid are represented in different chemical entities of natural origin [25,26]. A literature search revealed only four compounds with N-N-linked-phosphorous moiety including fosfazinomycins A and B from Streptomyces lavendofoliae [27], FR-900137 from Streptomyces unzenensis [28,29] and O,O-dipropyl (E)-2-(1-methyl-2-oxopropylidene)phosphorohydrazidothioate (E)-oxime) from the dinoflagellate Gymnodinium breve [30].…”