Computer-Assisted Engineering of Synthetic Pathway forBiodegradation of Toxic Persistent Pollutant.
2014
Anthropogenic halogenated compounds were unknown to Nature
until the industrial revolution, and microorganisms have not
had sufficient time to evolve enzymes for their degradation.
The lack of efficient enzymes and natural pathways can be
addressed through a combination of protein and metabolic
engineering. We have assembled a synthetic route for conversion
of the highly toxic and recalcitrant 1,2,3-trichloropropane to
glycerol in Escherichia coli, and used it for a systematic
study of pathway bottlenecks. Optimal ratios of enzymes for the
maximal production of glycerol, and minimal toxicity of
metabolites were predicted using a mathematical model. The
strains containing the expected optimal ratios of enzymes were
constructed and characterized for their viability and
degradation efficiency. Excellent agreement between predicted
and experimental data was observed. The validated model was
used to quantitatively describe the kinetic limitations of
currently available enzyme variants, and predict improvements
required for further pathway optimization. This highlights the
potential of forward engineering of microorganisms for the
degradation of toxic anthropogenic compounds.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI