Soil microorganisms participate in almost all soil organic carbon (SOC) transformations, but they are not represented explicitly in the current generation of earth system models. This study used a data-driven approach to incorporate extracellular enzyme activity into the Terrestrial ECOsystem (TECO) model, and the updated version was named the Data-driven ENZYme (DENZY) model. DENZY is based on results from an extensive data synthesis, which show that the CN ratio is positively correlated with ligninase activity (R2 = 0.50). The latter is inversely correlated to soil organic carbon storage. The DENZY model was parameterized using the revise database to information from a recent meta-analysis and tested for its ability to simulate SOC dynamics at Duke Forest (North Carolina, USA) from 1996 to 2007. DENZY can well simulate the observed negative relationship between ligninase activity and SOC under N deposition conditions (R2 ranges from 0.61 to 0.89). Moreover, outputs from DENZY better matched the observed SOC than its prototype model with the same parameterization. This study provides a simple and straightforward approach to effectively use real-world observations to improve SOC projections in terrestrial biogeochemical models.