Title: The underappreciated role of phosphonates in nature
Authors: Labeda DP, Yu X, Doroghazi JR, Janga S, Zhang J, Circello BT, Griffin BM, Metcalf WW
Journal: Proc Natl Acad Sci U S A
Accepted date: 2013 Nov 8
Interpretive summary: Phosphonates, molecules that contain directly linked carbon and phosphorus atoms, comprise an extremely diverse group of biologically produced compounds. The potential for production of these compounds in nature and the estimated range of all possible types of phosphonate-containing molecules that could be produced had not been done to date. Because it was known that one key enzyme, phosphoenolpyruvate mutase (pepM), is necessary for the biosynthesis of molecules containing the phosphonate structure we postulated that this gene could be used as a molecular marker to estimate ability to produce phosphonates. Genome sequences in public databases, including sequences determined from metagenomes, bulk DNA samples prepared from environment samples, as well as DNA prepared from a diverse set of microbial isolates were screened for the presence of the pepM gene resulting in the discovery that pepM is relatively common (5 to 7% positive), particularly in the actinomycetes, that are typical soil microorganisms. An estimate of the diversity of potentially novel compounds produced was obtained by sequencing the pepM gene and the 3 genes before and after it on chromosomal DNA from 25 different actinomycete strains and then comparing these sequences to the genome data in the public databases which confirmed that sequence of pepM could reliably predict the capability to produce different compounds. Evaluation of the number of different pepM sequences found in DNA isolated from local soils predicted that there were microorganisms present in the soil with the ability to produce dozens of potentially novel phosphonate-containing compounds, and the potential to produce hundreds of new phosphonate structures were observed in the public metagenome sequence databases from various environmental sources. These microbially-produced phosphonate-containing molecules could play an important role in the global cycling of phosphorus in soil and water and, more importantly, provide an untapped source of novel biologically active natural products with the potential for significant impact in agriculture or human and veterinary medicine.