PATHcre8: A Tool That Facilitates the Searching for Heterologous Biosynthetic Routes,ACS Synthetic Biology

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PATHcre8: A Tool That Facilitates the Searching for Heterologous Biosynthetic Routes
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-11-16 , DOI: 10.1021/acssynbio.0c00058
Olaa Motwalli _{1,

2} , Mahmut Uludag ₁ , Ivan Mijakovic _{3,

4} , Meshari Alazmi ₅ , Vladimir B. Bajic ₁ , Takashi Gojobori _{1,

6} , Xin Gao ₁ , Magbubah Essack ₁

Affiliation

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 PATH^cre8 to facilitate an optimized search for heterologous biosynthetic pathway routes. PATH^cre8 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 PATH^cre8 is more efficient in ranking functional pathways. To illustrate the effectiveness of PATH^cre8, we further provide case studies focused on isoprene production and the biodegradation of cocaine. PATH^cre8 is free for academic and nonprofit users and can be accessed at https://www.cbrc.kaust.edu.sa/pathcre8/.

中文翻译：

PATH ^cre8：一种有助于寻找异源生物合成途径的工具

开发能够促进细胞工厂合理设计，以更高的产量生产所需产品的合理计算工具具有挑战性，因为该工具需要考虑到首选宿主生物通常具有竞争性反应所消耗的化合物，从而降低了所需产量。产品。另一方面，优选的宿主生物可能不具有产生目的化合物所需的天然代谢反应。因此，计算工具需要识别将最有效地产生所需产物的代谢反应。在这方面，我们开发了通用工具PATH ^cre8，以促进对异源生物合成途径途径的优化搜索。路径^cre8在包括蓝细菌在内的许多生物体中发现并排序生物合成途径。该工具根据反映反应热力学的特征评分，途径中潜在的有毒产物（化合物毒性），竞争反应消耗的途径中的中间产物（产物消耗）以及特定于宿主的信息（例如酶拷贝数）对途径进行排名。与其他几个类似工具的比较表明，PATH ^cre8在对功能路径进行排序时效率更高。为了说明PATH ^cre8的有效性，我们进一步提供了有关异戊二烯生产和可卡因生物降解的案例研究。路径^cre8 对于学术和非营利性用户都是免费的，可以通过https://www.cbrc.kaust.edu.sa/pathcre8/进行访问。

更新日期：2020-12-18

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