PATHcre8: A Tool That Facilitates the Searching for Heterologous Biosynthetic Routes
AuthorsMotwalli, Olaa Amin
Bajic, Vladimir B.
KAUST DepartmentApplied Mathematics and Computational Science Program
Biological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Structural and Functional Bioinformatics Group
KAUST Grant NumberBAS/1/1059-01-01
Embargo End Date2021-11-17
Permanent link to this recordhttp://hdl.handle.net/10754/666037
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AbstractDeveloping 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/.
CitationMotwalli, 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.0c00058
SponsorsThis 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.
PublisherAmerican Chemical Society (ACS)
JournalACS Synthetic Biology
CollectionsArticles; 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) Division
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