In this paper, we propose a new end-to-end methodology to optimize the energy performance as well as comfort and air quality in large buildings without any renovation work. We introduce a metamodel based on recurrent neural networks and trained to predict the behavior of a general class of buildings using a database sampled from a simulation program. This metamodel is then deployed in different frameworks and its parameters are calibrated using the specific data of two real buildings. Parameters are estimated by comparing the predictions of the metamodel with real data obtained from sensors using the CMA-ES algorithm, a derivative free optimization procedure. Then, energy consumptions are optimized while maintaining a target thermal comfort and air quality, using the NSGA-II multi-objective optimization procedure. The numerical experiments illustrate how this metamodel ensures a significant gain in energy efficiency, up to almost 10%, while being computationally much more appealing than numerical models and flexible enough to be adapted to several types of buildings.