Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2319-24. doi: 10.1073/pnas.0712177105. Epub 2008 Feb 5.

Assessing the potential of mutational strategies to elicit new phenotypes in industrial strains.

Author information

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139, USA.


Industrial strains have been traditionally improved by rational approaches and combinatorial methods involving mutagenesis and selection. Recently, other methods have emerged, such as the use of artificial transcription factors and engineering of the native ones. As methods for generating genetic diversity continue to proliferate, the need for quantifying phenotypic diversity and, hence, assessing the potential of various genetic libraries for strain improvement becomes more pronounced. Here, we present a metric based on the quantification of phenotypic diversity, using Lactobacillus plantarum as a model organism. We found that phenotypic diversity can be introduced by mutagenesis of the principal sigma factor, that this diversity can be modulated by tuning the sequence diversity, and that this method compares favorably with commonly used protocols for chemical mutagenesis. The results of the diversity metric here developed also correlated well with the probability of finding improved mutants in the different libraries, as determined by recursive screening under stress. In addition, we subjected our libraries to lactic and inorganic acids and found strains with improved growth in both conditions, with a concomitant increase in lactate productivity.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk