The Tupelo semantic content management middleware implements Knowledge Spaces that enable scientists to locate, use, link, annotate, and discuss data and metadata as they work with existing applications in distributed environments. Tupelo is built using a combination of commonly-used Semantic Web technologies for metadata management, content management technologies for data management, and workflow technologies for management of computation, and can interoperate with other tools using a variety of standard interfaces and a client and desktop API. Tupelo's primary function is to facilitate interoperability, providing a Knowledge Space "view" of distributed, heterogeneous resources such as institutional repositories, relational databases, and semantic web stores. Knowledge Spaces have driven recent work creating e-Science cyberenvironments to serve distributed, active scientific communities. Tupelo-based components deployed in desktop applications, on portals, and in AJAX applications interoperate to allow researchers to develop, coordinate and share datasets, documents, and computational models, while preserving process documentation and other contextual information needed to produce a complete and coherent research record suitable for distribution and archiving.