compartmentalized self-replication under fast pcr cycling conditions yields taq dna polymerase mutants with increased dna-binding affinity and blood resistance

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ID: 217438
2014
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Ranked #714 of 875 articles by views in journal of magnetic resonance (san diego, calif : 1997)

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Abstract
Faster-cycling PCR formulations, protocols, and instruments have been developed to address the need for increased throughput and shorter turn-around times for PCR-based assays. Although run times can be cut by up to 50%, shorter cycle times have been correlated with lower detection sensitivity and increased variability. To address these concerns, we applied Compartmentalized Self Replication (CSR) to evolve faster-cycling mutants of Taq DNA polymerase. After five rounds of selection using progressively shorter PCR extension times, individual mutations identified in the fastest-cycling clones were randomly combined using ligation-based multi-site mutagenesis. The best-performing combinatorial mutants exhibit 35- to 90-fold higher affinity (lower Kd ) for primed template and a moderate (2-fold) increase in extension rate compared to wild-type Taq. Further characterization revealed that CSR-selected mutations provide increased resistance to inhibitors, and most notably, enable direct amplification from up to 65% whole blood. We discuss the contribution of individual mutations to fast-cycling and blood-resistant phenotypes.
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earezi2014frontierscompartmentalized Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Bahram eArezi;Nancy eMckinney;Connie eHansen;Michelle eCayouette;Jeffrey eFox;Keith eChen;Jennifer eLapira;Sarah eHamilton;Holly eHogrefe
Journal journal of magnetic resonance (san diego, calif : 1997)
Year 2014
DOI
10.3389/fmicb.2014.00408
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