ABSTRACT To support students’ agency in the process of constructing knowledge in a science classroom, it is important to design learning environments that allow students to shape knowledge building practices. In this paper, we present an Emergent Systems Microworld (ESM)-based learning environment called GenEvo, which is designed to ‘restructurate’ learning of fundamental ideas in modern biology, such as gene regulation. We study how cognitive, social, and affective properties of agent-based restructurations supported student learning. We report findings from a qualitative analysis of video data of student participation and interviews in the fourth iteration of a design-based research project about an ESM-based curricular unit. We discuss how specific design features of the ESM supported students’ epistemically agentive learning. Students of the GenEvo course shaped practices to investigate and construct knowledge about emergent biological phenomena and learned about emergent phenomena related to gene regulation and evolution. This work demonstrates how the properties of a restructuration make ESM-based learning environments effective for students to collectively shape knowledge building practices and learn about emergent phenomena.