The increase in enzymatic rates with temperature up to an optimum temperature (Topt) is widely attributed to classical Arrhenius behavior, with the decrease in enzymatic rates above Topt ascribed to protein denaturation and/or aggregation. This account persists despite many investigators noting that denaturation is insufficient to explain the decline in enzymatic rates above Topt. Here we show that it is the change in heat capacity associated with enzyme catalysis (ΔC(‡)p) and its effect on the temperature dependence of ΔG(‡) that determines the temperature dependence of enzyme activity. Through mutagenesis, we demonstrate that the Topt of an enzyme is correlated with ΔC(‡)p and that changes to ΔC(‡)p are sufficient to change Topt without affecting the catalytic rate. Furthermore, using X-ray crystallography and molecular dynamics simulations we reveal the molecular details underpinning these changes in ΔC(‡)p. The influence of ΔC(‡)p on enzymatic rates has implications for the temperature dependence of biological rates from enzymes to ecosystems.

Organic photovoltaics (OPVs) promise cheap and flexible solar energy. Whereas light generates free charges in silicon photovoltaics, excitons are normally formed in organic semiconductors due to their low dielectric constants, and require molecular heterojunctions to split into charges. Recent record efficiency OPVs utilise the small molecule, Y6, and its analogues, which – unlike previous organic semiconductors – have low band-gaps and high dielectric constants. We show that, in Y6 films, these factors lead to intrinsic free charge generation without a heterojunction. Intensity-dependent spectroscopy reveals that 60–90% of excitons form free charges at AM1.5 light intensity. Bimolecular recombination, and hole traps constrain single component Y6 photovoltaics to low efficiencies, but recombination is reduced by small quantities of donor. Quantum-chemical calculations reveal strong coupling between exciton and CT states, and an intermolecular polarisation pattern that drives exciton dissociation. Our results challenge how current OPVs operate, and renew the possibility of efficient single-component OPVs.

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The shikimate pathway is the biosynthetic route that is responsible for the production of essential aromatic compounds (1). These include the aromatic amino acids tryptophan, tyrosine, and phenylalanine, folic acid, an essential cofactor for many enzymatic processes, and salicylate, used for the biosynthesis of the siderophores through which bacteria acquire iron (2). The pathway is found in microorganisms and plants and has more recently been discovered in apicomplexan parasites (3, 4). The pathway is absent in higher organisms, making the enzymes of this pathway attractive as targets for the development of antimicrobial agents. Recent gene disruption studies have shown that operation of the shikimate pathway is essential for the viability of Mycobacterium tuberculosis (5), the causative agent of tuberculosis, a disease that remains a significant world-wide health risk (6). Although effective anti-tuberculosis drugs exist, the long treatment times required, the problems of latent or persistent tuberculosis (7), and the proliferation of multidrug-resistant strains of M. tuberculosis (8) have all created an urgent need for the development of new antimycobacterial agents.The first committed step in the shikimate pathway is the stereospecific aldol reaction between phosphoenolpyruvate (PEP) 4 and erythrose 4-phosphate (E4P) to produce 3-deoxy-Darabino-heptulosonate 7-phosphate (DAH7P), catalyzed by the enzyme DAH7P synthase (Fig. 1). DAH7P is converted into chorismate, the product of the main shikimate pathway, via six further enzyme-catalyzed reactions. At this point the pathway to the aromatic amino acids branches, with chorismate converted either to anthranilate by anthranilate synthase or to prephenate by chorismate mutase. Anthranilate ultimately produces Trp, whereas prephenate is converted into Phe and Tyr.As the first enzyme, DAH7P synthase, is a major control point for shikimate pathway flux. Several organisms express two or more isozymes of this enzyme that show different sensitivity to the pathway end products. Escherichia coli and Neurospora crassa each produce three isozymes, with each enzyme individually inhibited by either Phe, Tyr, or Trp (9,10

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