Project: Overcoming metabolic stochasticity and population dynamics in microbial cell factories.

The efficiency of industrial whole-cell production processes is most often afflicted by the formation of subpopulations in a microbial culture during biotransformations and fermentations. A bioreactor running in batch, fed-batch or continuous mode can be regarded as an artificial environment that is permanently changing [CurrOpMicrobiol 2000, 3:248] and thus creating a diversity of functional microhabitats which ultimately lead to the emergence of various pheno- and genotypes [BiotechBioeng 2010, 105:705]. Phenotypic heterogeneity and variability represents a key -and unwanted feature in the bacterial population that constitutes the biological catalyst. This project will investigate the phenomena of metabolic stochasticity and population dynamics in microbial cell factories using Pseudomonas sp. growing in suspended culture, as well as attached to surfaces as catalytic biofilms. Biofilms are resilient to a wide variety of environmental stresses. This inherited robustness make biofilms desirable as potent biocatalysts, especially regarding reactions involving biological difficult substrates and/or products [TrendsBiotechnol 2009, 27:636]. This project addresses the phenomenon of catalytic heterogeneity of genetically identical bacterial cells using a controllable system composed of non-pathogenic Pseudomonas strains as host of reference. The biosynthesis of the short chain alcohol isobutanol will be employed as a model reaction system. On the technical side, cultivation systems and molecular tools will be developed for analyzing catalytic heterogeneity in bacterial cultures under process conditions (i). Following identification of process relevant subpopulations (ii), the responsible signals and molecular mechanisms controlling the formation of the respective mutations will be identified (iii) and strategies to guide phenotypic and genotypic heterogeneity throughout an entire population will be developed (iv). The main outcome of this project is a collection of Pseudomonas strains (CONTIbugs) optimized as cell factories for hosting and stably expressing heterologous genes and maintaining productive catalytic activities in controlled populations for industrial biotechnology.

Acronym CONTIbugs
Duration 01/01/2013 - 31/12/2016
Website visit project website
Network ERA-IB-2
Call 3rd ERA-IB Joint Call

Project partner

Number Name Role Country
Tel Aviv University - School of Medicine & School of Computer Science Israel
Technical University of DK - Department of Systems biology, Center for Systems Microbiology, Infection Microbiology Group Denmark
Technical University of Dortmund - Laboratory of Chemical Biotechnology Coordinator Germany
Spanish National Research Council - Spanish National Center for Biotechnology Spain