Computer Science, College of Engineering, Mathematics, and Physical Sciences, University of Exeter, Exeter EX4 4QF, UK.
Nucleic Acids Res. 2013 Jun;41(11):e113. doi: 10.1093/nar/gkt234. Epub 2013 Apr 10.
One of the primary aims of synthetic biology is to (re)design metabolic pathways towards the production of desired chemicals. The fast pace of developments in molecular biology increasingly makes it possible to experimentally redesign existing pathways and implement de novo ones in microbes or using in vitro platforms. For such experimental studies, the bottleneck is shifting from implementation of pathways towards their initial design. Here, we present an online tool called 'Metabolic Tinker', which aims to guide the design of synthetic metabolic pathways between any two desired compounds. Given two user-defined 'target' and 'source' compounds, Metabolic Tinker searches for thermodynamically feasible paths in the entire known metabolic universe using a tailored heuristic search strategy. Compared with similar graph-based search tools, Metabolic Tinker returns a larger number of possible paths owing to its broad search base and fast heuristic, and provides for the first time thermodynamic feasibility information for the discovered paths. Metabolic Tinker is available as a web service at http://osslab.ex.ac.uk/tinker.aspx. The same website also provides the source code for Metabolic Tinker, allowing it to be developed further or run on personal machines for specific applications.
合成生物学的主要目标之一是(重新)设计代谢途径,以生产所需的化学物质。分子生物学的快速发展使得在微生物中或使用体外平台上实验性地重新设计现有途径和实施全新途径变得越来越可行。对于此类实验研究,瓶颈正从途径的实施转移到其最初的设计上。在这里,我们介绍了一个名为“代谢 tinkerer”的在线工具,它旨在指导在任何两个所需化合物之间设计合成代谢途径。给定两个用户定义的“目标”和“源”化合物,代谢 tinkerer 使用定制的启发式搜索策略在整个已知的代谢宇宙中搜索热力学可行的路径。与类似的基于图的搜索工具相比,代谢 tinkerer 由于其广泛的搜索基础和快速的启发式搜索,返回了更多可能的路径,并首次为发现的路径提供了热力学可行性信息。代谢 tinkerer 可作为网络服务在 http://osslab.ex.ac.uk/tinker.aspx 上使用。同一网站还提供了代谢 tinkerer 的源代码,允许对其进行进一步开发,或在个人机器上针对特定应用程序运行。