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A genomics approach to improve the analysis and design of strain selections

Paper ID Volume ID Publish Year Pages File Format Full-Text
31864 44846 2008 12 PDF Available
Title
A genomics approach to improve the analysis and design of strain selections
Abstract

Strain engineering has been traditionally centered on the use of mutation, selection, and screening to develop improved strains. Although mutational and screening methods are well-characterized, selection remains poorly understood. We hypothesized that we could use a genome-wide method for assessing laboratory selections to design selections with enhanced sensitivity (true positives) and specificity (true negatives) towards a single desired phenotype. To test this hypothesis, we first applied multi-SCale Analysis of Library Enrichments (SCALEs) to identify genes conferring increased fitness in continuous flow selections with increasing levels of 3-hydroxypropionic acid (3-HP). We found that this selection not only enriched for 3-HP tolerance phenotypes but also for wall adherence phenotypes (41% false positives). Using this genome-wide data, we designed a serial-batch selection with a decreasing 3-HP gradient. Further examination by ROC analysis confirmed that the serial-batch approach resulted in significantly increased sensitivity (46%) and specificity (10%) for our desired phenotype (3-HP tolerance).

Keywords
3-Hydroxypropionic acid; Tolerance; Selection; Strain engineering; Multi-SCale Analysis of Library Enrichments (SCALEs)
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 10, Issues 3–4, May–July 2008, Pages 154–165
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us