摘要：SummaryMechanistic models of biochemical systems provide a rigorous description of biological phenomena. They are indispensable for making predictions and elucidating biological design principles. To date, mathematical analysis and characterization of these models encounter a bottleneck consisting of large numbers of unknown parameter values. Here, we introduce the Design Space Toolbox v.3.0 (DST3), a software implementation of the Design Space formalism enabling mechanistic modeling without requiring previous knowledge of parameter values. This is achieved by using a phenotype-centric modeling approach, in which the system is first decomposed into a series of biochemical phenotypes. Parameter values realizing phenotypes of interest are subsequently predicted. DST3 represents the most generally applicable implementation of the Design Space formalism and offers unique advantages over earlier versions. By expanding the Design Space formalism and streamlining its distribution, DST3 represents a valuable tool for elucidating biological design principles and designing novel synthetic circuits.Graphical AbstractDisplay OmittedHighlights•DST3 extends the Design Space formalism by identifying additional phenotypes•Additional phenotypes arise from cycles, conservations, and metabolic imbalances•DST3 enables mechanistic modeling without previous knowledge of parameter values•It fully unlocks the potential of the novel phenotype-centric modeling strategyBiological Sciences; Systems Biology; In Silico Biology
