EcoSynther: A Customized Platform To Explore the Biosynthetic Potential in <i>E. coli</i>

Developing computational
tools for a chassis-centered biosynthetic
pathway design is very important for a productive heterologous biosynthesis
system by considering enormous foreign biosynthetic reactions. For
many cases, a pathway to produce a target molecule consists of both
native and heterologous reactions when utilizing a microbial organism
as the host organism. Due to tens of thousands of biosynthetic reactions
existing in nature, it is not trivial to identify which could be served
as heterologous ones to produce the target molecule in a specific
organism. In the present work, we integrate more than 10,000 E. coli non-native reactions and utilize a probability-based
algorithm to search pathways. Moreover, we built a user-friendly Web
server named EcoSynther. It is able to explore the precursors and
heterologous reactions needed to produce a target molecule in Escherichia coli K12 MG1655 and then applies flux balance
analysis to calculate theoretical yields of each candidate pathway.
Compared with other chassis-centered biosynthetic pathway design tools,
EcoSynther has two unique features: (1) allow for automatic search
without knowing a precursor in E. coli and (2) evaluate
the candidate pathways under constraints from E. coli physiological states and growth conditions. EcoSynther is available
at http://www.rxnfinder.org/ecosynther/.

开发以底盘为中心的生物合成途径设计计算工具，对于构建高效异源生物合成系统至关重要——这是因为自然界中存在海量外源生物合成反应。在多数情况下，以微生物作为宿主生物时，目标分子的合成途径同时包含内源与异源反应。自然界中现存数万种生物合成反应，因此要筛选出可在特定宿主生物中合成目标分子的异源反应，并非易事。
本研究整合了超过10000个大肠杆菌（E. coli）非内源反应，并采用基于概率的算法开展途径搜索。此外，我们构建了一款用户友好的Web服务器，命名为EcoSynther。该工具可探索在大肠杆菌K12 MG1655（Escherichia coli K12 MG1655）中合成目标分子所需的前体物质与异源反应，并通过通量平衡分析（Flux Balance Analysis）计算每条候选途径的理论产率。
与其他以底盘为中心的生物合成途径设计工具相比，EcoSynther具备两项独特优势：（1）无需预先知晓大肠杆菌内的前体物质即可实现自动途径搜索；（2）可结合大肠杆菌生理状态与生长条件的约束条件对候选途径进行评估。EcoSynther的访问地址为http://www.rxnfinder.org/ecosynther/