Here, we developed a methodology to simultaneously inactivate multiple enzymes by targeting a common post-translational modification system, simplifying strain construction by minimizing the necessary genetic modifications.
Of particular interest here is the use of DNAzymes that can undergo the so-called enzymatic cascade reactions, where the activation of multiple enzymes by a target DNA can result in ultra-sensitivity, comparable many PCR based assays.
2-arachidonoylglycerol has been reported to be hydrolysed by multiple enzyme activities from neural preparations, including ABHD6 (Q9BV23) 197, ABHD12 (8neuropathy neuropatargetrgesterasease (PNPLA6, Q8IY17 204) and carboxylesterase 1 (CES1, P23141 212).
In summary, our study provided a practical drug design strategy targeting multiple enzymes, and 15a represents a novel and promising lead compound for the development of novel epigenetic inhibitors as antitumor agents.
To effectively channel the glycans one may have to resort to changing the levels of multiple enzymes depending on the target glycan.
PUGNAc is a promiscuous inhibitor, targeting multiple enzymes from functionally related glycoside hydrolase families, including retaining α- and β-glucosaminidases from GH89 and GH3, respectively [26,27].
Highly enriched subsets of HIF-1α ChIP hits included multiple enzymes of the glycolytic pathway, autophagic targets and jumonji domain (JmjC) containing histone demethylases.
This supports the hypothesis that the HATs play partly redundant roles in gene regulation, with multiple enzymes contributing to expression of common targets.
If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance.
The dramatic increase in ethanol production suggests that targeting protein post-translational modification is a promising new approach for simultaneous inactivation of multiple enzymes.
