PATHcre8: A Tool That Facilitates the Searching for Heterologous Biosynthetic Routes
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ArticleAuthors
Motwalli, Olaa Amin
Uludag, Mahmut

Mijakovic, Ivan

Alazmi, Meshari

Bajic, Vladimir B.

Gojobori, Takashi

Gao, Xin

Essack, Magbubah

KAUST Department
Applied Mathematics and Computational Science ProgramBiological and Environmental Sciences and Engineering (BESE) Division
Bioscience Program
Computational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Structural and Functional Bioinformatics Group
KAUST Grant Number
BAS/1/1059-01-01BAS/1/1606-01-01
BAS/1/1624-01-01
FCC/1/1976-02-01
FCC/1/1976-17-01
FCC/1/1976-26-01
Date
2020-11-16Embargo End Date
2021-11-17Submitted Date
2020-02-02Permanent link to this record
http://hdl.handle.net/10754/666037
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Developing computational tools that can facilitate the rational design of cell factories producing desired products at increased yields is challenging, as the tool needs to take into account that the preferred host organism usually has compounds that are consumed by competing reactions that reduce the yield of the desired product. On the other hand, the preferred host organisms may not have the native metabolic reactions needed to produce the compound of interest; thus, the computational tool needs to identify the metabolic reactions that will most efficiently produce the desired product. In this regard, we developed the generic tool PATHcre8 to facilitate an optimized search for heterologous biosynthetic pathway routes. PATHcre8 finds and ranks biosynthesis routes in a large number of organisms, including Cyanobacteria. The tool ranks the pathways based on feature scores that reflect reaction thermodynamics, the potentially toxic products in the pathway (compound toxicity), intermediate products in the pathway consumed by competing reactions (product consumption), and host-specific information such as enzyme copy number. A comparison with several other similar tools shows that PATHcre8 is more efficient in ranking functional pathways. To illustrate the effectiveness of PATHcre8, we further provide case studies focused on isoprene production and the biodegradation of cocaine. PATHcre8 is free for academic and nonprofit users and can be accessed at https://www.cbrc.kaust.edu.sa/pathcre8/.Citation
Motwalli, O., Uludag, M., Mijakovic, I., Alazmi, M., Bajic, V. B., Gojobori, T., … Essack, M. (2020). PATHcre8: A Tool That Facilitates the Searching for Heterologous Biosynthetic Routes. ACS Synthetic Biology. doi:10.1021/acssynbio.0c00058Sponsors
This work has been supported by the King Abdullah University of Science and Technology (KAUST) Base Research Fund BAS/1/1606-01-01, BAS/1/1059-01-01, BAS/1/1624-01-01, as well as through the Awards No. FCC/1/1976-02-01, FCC/1/1976-17-01, FCC/1/1976-16-01, and FCC/1/1976-26-01 from the KAUST Office of Sponsored Research (OSR). Also, the Novo Nordisk Foundation Grant NNF10CC1016517 awarded to IM.Publisher
American Chemical Society (ACS)Journal
ACS Synthetic BiologyPubMed ID
33198455Additional Links
https://pubs.acs.org/doi/10.1021/acssynbio.0c00058ae974a485f413a2113503eed53cd6c53
10.1021/acssynbio.0c00058
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Articles; Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Applied Mathematics and Computational Science Program; Structural and Functional Bioinformatics Group; Computer Science Program; Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) DivisionRelated articles
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