Phosphonates represent an important source of bioavailable phosphorus in certain environments. Accordingly, many microorganisms (particularly marine bacteria) possess catabolic pathways to degrade these molecules. One example is the widespread hydrolytic route for the breakdown of 2-aminoethylphosphonate (AEP, the most common biogenic phosphonate). In this pathway, the aminotransferase PhnW initially converts AEP into phosphonoacetaldehyde (PAA), which is then cleaved by the hydrolase PhnX to yield acetaldehyde and phosphate. This work focuses on a pyridoxal 5′-phosphate-dependent enzyme that is encoded in >13% of the bacterial gene clusters containing the phnW–phnX combination. This enzyme (which we termed PbfA) is annotated as a transaminase, but there is no obvious need for an additional transamination reaction in the established AEP degradation pathway. We report here that PbfA from the marine bacterium Vibrio splendidus catalyzes an elimination reaction on the naturally occurring compound ( R )-1-hydroxy-2-aminoethylphosphonate ( R -HAEP). The reaction releases ammonia and generates PAA, which can be then hydrolyzed by PhnX. In contrast, PbfA is not active toward the S enantiomer of HAEP or other HAEP-related compounds such as ethanolamine and d , l -isoserine, indicating a very high substrate specificity. We also show that R -HAEP (despite being structurally similar to AEP) is not processed efficiently by the PhnW–PhnX couple in the absence of PbfA. In summary, the reaction catalyzed by PbfA serves to funnel R -HAEP into the hydrolytic pathway for AEP degradation, expanding the scope and the usefulness of the pathway itself.

The fungal metabolite Fosfonochlorin features a chloroacetyl moiety that is unusual within known phosphonate natural product biochemistry. Putative biosynthetic genes encoding Fosfonochlorin in Fusarium and Talaromyces spp. were investigated through reactions of encoded enzymes with synthetic substrates and isotope labelling studies. We show that the early biosynthetic steps for Fosfonochlorin involve the reduction of phosphonoacetaldehyde to form 2-hydroxyethylphosphonic acid, followed by oxidative intramolecular cyclization of the resulting alcohol to form (S)-epoxyethylphosphonic acid. The latter reaction is catalyzed by FfnD, a rare example of a nonheme iron/2-(oxo)glutarate dependent oxacyclase. In contrast, FfnD behaves as a more typical oxygenase with ethylphosphonic acid, producing (S)-1-hydroxyethylphosphonic acid. FfnD thus represents a new example of a ferryl generating enzyme that can suppress the typical oxygen rebound reaction that follows abstraction of a substrate hydrogen by a ferryl oxygen, thereby directing the substrate radical towards a fate other than hydroxylation.

Phosphonic acids are highly stable phosphorus-containing compounds, which have been proposed as important intermediates in the global phosphorus cycle. Biogenic phosphonates as well as their synthetic analogues play an important role as potential enzyme inhibitor drugs and as alternative phosphorus source for microbes. Despite these properties, their metabolism is still poorly understood. New degradative pathways and unknown compounds are identified at fast pace. However, most of these pathways include a variety of unique enzymatic transformations, which are difficult to characterize – especially without sufficient amounts of the potential substrates and intermediates of the postulated transformations in hands. Thus, there is a great need for the development of synthetic methodologies to access phosphonic acids in high yields and in enantiomerically pure form for the use in enzymatic studies and in studies on the biological activity of newly isolated natural products, which are often only obtained in low yields. In this Synpacts article we aim at highlighting our recent contributions to this field.1 Introduction2 Phosphonates as Alternative Phosphorus Source3 The Application of Phosphonates in Enzymatic Studies4 Conclusion

The bioprotective nature of monosaccharides and disaccharides is often attributed to their ability to slow down the dynamics of adjacent water molecules. Indeed, solvation dynamics close to sugars is indisputably retarded compared to bulk water. However, further research is needed on the qualitative and quantitative differences between the water dynamics around different saccharides. Current studies on this topic disagree on whether the disaccharide trehalose retards water to a larger extent than other isomers. Based on molecular dynamics simulation of the time-dependent Stokes shift of a chromophore close to the saccharides trehalose, sucrose, maltose, and glucose, this study reports a slightly stronger retardation of trehalose compared to other sugars at room temperature and below. Calculation and analysis of the intermolecular nuclear Overhauser effect, nuclear quadrupole relaxation, dielectric relaxation spectroscopy, and first shell residence times at room temperature yield further insights into the hydration dynamics of different sugars and confirm that trehalose slows down water dynamics to a slightly larger extent than other sugars. Since the calculated observables span a wide range of timescales relevant to intermolecular nuclear motion, and correspond to different kinds of motions, this study allows for a comprehensive view on sugar hydration dynamics.

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