This is a "maybe" issue, but some elements of PEP 249 have already been implicitly coded into the codebase, such as synapse.storage.types, however, it could be easier to directly work with PEP 249's DB-API-v2 schema and approach to simplify the storage framework even further, and make (potential) future database engines easier to support.

(Things such as module .threadsafety properties can maybe help futher granularize database pooling mechanisms dynamically.)