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

J 2014

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

KURUMBANG, Nagendra Prasad, Pavel DVOŘÁK, Jaroslav BENDL, Jan BREZOVSKÝ, Zbyněk PROKOP et. al.

Základní údaje

Originální název

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

Autoři

KURUMBANG, Nagendra Prasad (524 Nepál, domácí), Pavel DVOŘÁK (203 Česká republika, domácí), Jaroslav BENDL (203 Česká republika, domácí), Jan BREZOVSKÝ (203 Česká republika, domácí), Zbyněk PROKOP (203 Česká republika, domácí) a Jiří DAMBORSKÝ (203 Česká republika, garant, domácí)

Vydání

ACS Synthetic Biology, 2014, 2161-5063

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.978

Kód RIV

RIV/00216224:14310/14:00074211

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1021/sb400147n

UT WoS

000333476900009

Klíčová slova anglicky

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

Štítky

AKR, rivok

Změněno: 21. 3. 2017 08:03, prof. Mgr. Jiří Damborský, Dr.

Anotace

V originále

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.

Návaznosti

ED0001/01/01, projekt VaV

Název: CETOCOEN

EE2.3.30.0037, projekt VaV

Název: Zaměstnáním nejlepších mladých vědců k rozvoji mezinárodní spolupráce

GAP503/12/0572, projekt VaV

Název: Konstrukce syntetické metabolické dráhy pro degradaci důležitého environmentálního polutantu proteinovým a metabolickým inženýrstvím

Investor: Grantová agentura ČR, Konstrukce syntetické metabolické dráhy pro degradaci důležitého environmentlního polutantu proteinovým a metabolickým inženýrstvím

Citovat

KURUMBANG, Nagendra Prasad, Pavel DVOŘÁK, Jaroslav BENDL, Jan BREZOVSKÝ, Zbyněk PROKOP a Jiří DAMBORSKÝ. Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant. ACS Synthetic Biology. 2014, roč. 3, č. 3, s. 172-181. ISSN 2161-5063. Dostupné z: https://dx.doi.org/10.1021/sb400147n.

@article{1213471,
   author = {Kurumbang, Nagendra Prasad and Dvořák, Pavel and Bendl, Jaroslav and Brezovský, Jan and Prokop, Zbyněk and Damborský, Jiří},
   article_number = {3},
   doi = {http://dx.doi.org/10.1021/sb400147n},
   keywords = {activity; enantioselectivity; kinetic modeling; protein and metabolic engineering;synthetic pathway; toxicity},
   language = {eng},
   issn = {2161-5063},
   journal = {ACS Synthetic Biology},
   title = {Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant.},
   volume = {3},
   year = {2014}
}

TY  - JOUR
ID  - 1213471
AU  - Kurumbang, Nagendra Prasad - Dvořák, Pavel - Bendl, Jaroslav - Brezovský, Jan - Prokop, Zbyněk - Damborský, Jiří
PY  - 2014
TI  - Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant.
JF  - ACS Synthetic Biology
VL  - 3
IS  - 3
SP  - 172-181
EP  - 172-181
SN  - 21615063
KW  - activity
KW  - enantioselectivity
KW  - kinetic modeling
KW  - protein and metabolic engineering;synthetic pathway
KW  - toxicity
N2  - 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.
ER  -

KURUMBANG, Nagendra Prasad, Pavel DVOŘÁK, Jaroslav BENDL, Jan BREZOVSKÝ, Zbyněk PROKOP a Jiří DAMBORSKÝ. Computer-Assisted Engineering of Synthetic Pathway for Biodegradation of Toxic Persistent Pollutant. \textit{ACS Synthetic Biology}. 2014, roč.~3, č.~3, s.~172-181. ISSN~2161-5063. Dostupné z: https://dx.doi.org/10.1021/sb400147n.

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