Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • The MOF system described by

    2020-02-08

    The MOF system described by Farha and coworkers combines rational design of the support and good experimental results regarding activity and stability. However, a further increase in the speed of enzyme loading into the MOF and a decrease in leaching are still required. How can the design rules proposed here provide further leads to these improvements? Of the two parameters mentioned to influence enzyme uptake and release, i.e., pore-size matching and matrix-enzyme interactions, the former influences only the kinetics, whereas the latter can provide a stronger thermodynamic affinity. A possible solution, therefore, is replacing the organic linkers with more optimal hydrophobicity or using stronger covalent and non-covalent binding strategies to make the system function more as a sponge for the enzyme. However, an optimum can also be expected in this strategy, given that strong binding can decrease the total loading capacity as a result of premature blocking of the channels. Other alternatives could be the immobilization and anchoring of the enzyme during MOF synthesis or after in-diffusion in the form of physical or chemical entrapment after enzyme loading. The latter can possibly be achieved by end-capping the crystal with other ligands or by encapsulating the whole MOF-enzyme particle in yet another matrix that does not permit out-diffusion of the enzyme. In general, employing MOFs as enzyme supports yields the promise of stabilizing enzymes, thus making catalytic reactions performed by Erlotinib Hydrochloride function more reproducibly. This can give significant improvements for enzyme assays or for biocatalysis in industry. Think of, for example, using this system to stabilize horse radish peroxidase during blotting experiments. This method could also pave the way for enzyme-MOFs as reusable catalysts in organic synthesis or in sensors, in which enzymes often play a role in signal amplification. When the current challenges are overcome, the versatile and functionalizable structures of MOFs hold great promise for improving enzymes, making them ever more useful catalysts also outside living systems.
    Many Metabolic Enzymes Are Not Strictly Substrate-Specific It is now well appreciated that a substantial fraction of metabolic enzymes can catalyze reactions of different types and/or with different substrates 1, 2. The former behavior is termed catalytic promiscuity [3], the latter is usually called substrate promiscuity [4] (because these terms may be equivocal, Box 1 explains the definition of ‘promiscuity’ used here and compares it to a stricter definition accepted by evolutionary biochemists). Although this paper is essentially concerned with substrate promiscuity, it must be noted that the two behaviors are interrelated, often co-occur (e.g., 5, 6, 7), and have analogous impacts on metabolism, such that most points raised concerning substrate promiscuity are similarly applicable to catalytic promiscuity. Why is it that many metabolic enzymes can transform several different substrates? Is it simply because an absolute substrate specificity cannot be attained owing to the inherent imperfection of enzymes 8, 9? Or is it mostly Erlotinib Hydrochloride the result of selective pressures (or lack thereof)? Finally, what are the consequences and implications of the recurrence of substrate promiscuity for the global evolution of metabolism? Related to these issues, this review begins by showing that substrate specificity is indeed inherently limited, for reasons rooted in physical chemistry, but also that, in many cases, metabolic enzymes are less selective than they could be. The review then examines how different evolutionary factors (both positive and negative selection, as well as neutral drift) may help to shape the degree to which enzymes discriminate between potential substrates. Finally, it is suggested that the universal tendency of enzymes to show substrate promiscuity is an important source of metabolome complexity that helps to fuel an ‘underground’ network of reactions which may represent a basis for further evolution and diversification of metabolism.