Identification of malic enzyme mutants depending on 1,2,3-triazole moiety-containing nicotinamide adenine dinucleotide analogs.
Bioorganic & medicinal chemistry letters
confidence
Key findings
Identified ME mutants capable of using 1,2,3-triazole-containing NAD analogs as cofactor; no clinical/biological endpoints reported.
View source on PubMed (PMID 24513047) ↗
- Sample size
- Not reported
- Population
- In vitro enzyme mutants (malic enzyme)
- Dosing
- Not reported
- Duration
- Not reported
- Route
- In vitro
- Blinding
- not_reported
- Controls
- not_reported
- Drug class
- coenzyme
Full abstract
An activity screening between 1,2,3-triazole moiety-containing nicotinamide adenine dinucleotide (NAD) analogs and malic enzyme (ME) mutants identified some mutants capable of taking NAD analogs as the cofactor. One particular pair, ME-L310K/L404S and the analog B-8 had good catalytic efficiency and cofactor specificity. The new system gained about 1200-fold cofactor specificity shift from NAD toward B-8 in terms of oxidative decarboxylation of l-malate. Our results provided insightful information for the development of orthogonal redox system that is of particular important to precisely control engineered metabolic pathways.