Formal substitution of one of the four P–O bonds by a P–S bond generates thiophosphoric acid (H₃PO₃S). To date there is no indication that the parent inorganic thiophosphate is a known natural metabolite. On the other hand, a thiophosphate version of the internucleotide phosphodiester bond in bacterial DNA has been identified as a possible host defense system in several strains of bacteria. Only the S_P-diastereomer is observed. Its mode of formation is not from free inorganic thiophosphate but presumptively from a formal sequence specific substitution of existing internucleotide phosphodiester bonds in host bacterial DNA via persulfide anion enzyme chemistry. In a different context, chiral thiophosphoryl versions of ATP–alpha-S and ATP–gamma-¹⁸O,S have permitted determination of the stereochemistry of enzymatic nucleotidyl and phosphoryl transfers, respectively.