Catalysis for coal conversion (Тексты по английскому языку)

Life's phosphorous paradox

29 April 2010

Mike Blackburn, Jon Waltho and colleagues at the University of Sheffield, UK, discuss the important and diverse roles that phosphorus plays in all life forms. 

Evolution has placed phosphate esters at the heart of biology. From providing the extremely stable backbone of RNA and DNA to protein regulation by rapid catalytic reactions, they are one of the most remarkable features of chemistry in the body. 

Since the discovery of the structure of DNA by Crick and Watson in 1953, the stability of its backbone phosphate diester linkage has been identified as key to the durability of our genomic material. A durability that has allowed decoding of DNA from the mummy of Tutankhamun, some 3320 years old. Recent research has put the stability of a dialkyl phosphate ester under physiological conditions at a half-life of 100 million years and nucleic acids are intrinsically the most stable biopolymers in terrestrial biology. 

Phosphate monoesters are even more stable. They play important roles in compartmentalisation and transport regulation of water-soluble metabolites and in lipid membranes. Current estimates put the half-life of such esters at a billion years. Thirty years ago, the chemical basis of such stability was broadly linked to the intrinsic anionic character of a phosphate diester at physiological pH (a phosphate monoester being dianionic). This caused speculation that neutral diesters, such as sulfates, are not fitted for the biological task. 

Phosphate esters could play an important role in life throughout the whole universe

In contrast, a majority of all proteins have their behaviour modulated by the addition of a phosphate ester function or its removal occurring on a millisecond timescale. This role of rapid phosphorylation (kinase action) and dephosphorylation (phosphatase activity) is crucial in all living organisms. So this is the phosphate paradox in the evolution of life: extreme stability versus rapid manipulability. 

Over the last fifteen years, our understanding of how enzymes catalyse the formation and hydrolysis of phosphate esters has advanced considerably, especially through high resolution structures of models of their transition states based on the use of metal fluorides. Most generally, tetrafluoro-aluminate (AlF₄^-) forms octahedral complexes with donor and acceptor oxygens that closely mimic the trigonal bipyramidal transition state generally held to dominate phosphoryl transfer processes. But, the inability of X-ray crystallography to distinguish between oxygen and fluorine at the resolution of protein structures has made identification of fluoride speculative. This inherent problem has recently been overcome by applying high field ¹⁹F NMR spectroscopy to provide direct analysis of transition state complexes.    

An immediate success has been the identification of a trigonal bipyramidal complex for three different classes of phosphoryl transfer enzymes, a kinase, a mutase, and a phosphatase, that is centred on trifluoromagnesate (MgF₃^-). MgF₃^- is a near ideal analogue of the transferring phosphoryl entity, being isosteric and isoelectronic with PO₃^-. The additional discovery that depletion of the positive charge in the protein active site by one unit, typically through mutation of lysine or arginine to a neutral residue, elicits the response of unit charge decrease in the metal fluoride in the transition state analogue, typically MgF₃^- to AlF₃⁰. This provides direct experimental evidence for the opinion that the negative charge on phosphate esters provides the key to their essential biological stability, while its exact neutralisation is a major feature of the ability of enzymes to manipulate phosphate esters as necessary. With this insight, it is possible to review the potential of other oxyacids as alternatives to phosphate esters in life - but there is no evident alternative to phosphate! Esters of Group V elements such as vanadate and arsenate do not have the required stability and although sulfate monoesters have useful stability they are not in the league of phosphate monoesters. 

The Laws of Physics are universal, therefore Mendeleev's Periodic Table is equally universal and life anywhere in the universe must be based on the same elements, albeit tuned to variations in their abundances. Water can support life on earth from pH 0 to 12 and from -2°C to + 115°C at the extreme and it appears to be the indispensable liquid phase for life in the planetary habitable zone. It is a small additional step to conclude that phosphate esters and anhydrides will fulfil the same roles in life wherever it exists in this universe. 

Article citation: Matthew W. Bowler, New J. Chem., 2010, DOI: 10.1039/b9nj00718k

Why did Nature select phosphate for its dominant roles in biology?

Matthew W. Bowler, Matthew J. Cliff, Jonathan P. Waltho and G. Michael Blackburn

Evolution has placed phosphate mono- and diesters at the heart of biology. The enormous diversity of their roles has called for the evolution of enzyme catalysts for phosphoryl transfer that are among the most proficient known. A combination of high-resolution X-ray structure analysis and ¹⁹F NMR definition of metal fluoride complexes of such enzymes, that are mimics of the transition state for the reactions catalysed, has delivered atomic detail of the nature of such catalysis for a range of phosphoryl transfer processes. The catalytic simplicity thus revealed largely explains the paradox of the contrast between the extreme stability of structural phosphate esters and the lability of phosphates in regulation and signalling processes. A brief survey of the properties of oxyacids and their esters for other candidate elements for these vital roles fails to identify a suitable alternative to phosphorus, thereby underpinning Todd s Hypothesis Where there s life there s phosphorus as a statement of truly universal validity.