Publication Details

Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant

KURUMBANG Nagendra, DVOŘÁK Pavel, BENDL Jaroslav, BREZOVSKÝ Jan, PROKOP Zbyněk and DAMBORSKÝ Jiří. Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant. ACS Synthetic Biology, vol. 3, no. 3, 2014, pp. 172-181. ISSN 2161-5063. Available from: http://pubs.acs.org/doi/pdf/10.1021/sb400147n
Czech title
Počítačové modelování syntetické dráhy pro biodegradaci toxických látek
Type
journal article
Language
english
Authors
Kurumbang Nagendra, Ph.D. (LL)
Dvořák Pavel, Mgr. (LL)
Bendl Jaroslav, Ing., Ph.D. (FIT BUT)
Brezovský Jan, Mgr., Ph.D. (LL)
Prokop Zbyněk, doc. RnDr., Ph.D. (LL)
Damborský Jiří, prof. Mgr., Dr. (LL)
URL
Keywords


activity, enantioselectivity, kinetic modeling, protein and metabolic engineering, synthetic pathway, toxicity

Abstract

Anthropogenic halogenated compounds had been unknown to the nature until industrial revolution and microorganisms have not had sufficient time to evolve enzymes for their degradation. The lack of efficient enzymes and natural metabolic pathways can be addressed by combination of protein and metabolic engineering. We have assembled a synthetic pathway for conversion of highly toxic and recalcitrant 1,2,3-trichloropropane to glycerol in Escherichia coli and used it for systematic study of pathway bottlenecks. The optimal ratios of enzymes for maximal production of glycerol and minimal toxicity of metabolites were predicted using a mathematical model. The strains containing predicted ratios of enzymes were constructed and characterized for their viability and degradation efficiency. An excellent agreement between predicted and experimental data has been observed. The validated model has been used to quantitatively describe the kinetic limitations of currently available enzyme variants and predict the improvements required for further pathway optimization. Presented concept highlights the potential of rigorous rational engineering of microorganisms for degradation of toxic anthropogenic compounds.

Published
2014
Pages
172-181
Journal
ACS Synthetic Biology, vol. 3, no. 3, ISSN 2161-5063
Publisher
American Chemical Society
DOI
UT WoS
000333476900009
EID Scopus
BibTeX
@ARTICLE{FITPUB10462,
   author = "Nagendra Kurumbang and Pavel Dvo\v{r}\'{a}k and Jaroslav Bendl and Jan Brezovsk\'{y} and Zbyn\v{e}k Prokop and Ji\v{r}\'{i} Damborsk\'{y}",
   title = "Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant",
   pages = "172--181",
   journal = "ACS Synthetic Biology",
   volume = 3,
   number = 3,
   year = 2014,
   ISSN = "2161-5063",
   doi = "10.1021/sb400147n",
   language = "english",
   url = "https://www.fit.vut.cz/research/publication/10462"
}
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