While many advantages can be offered by DC-based integrated power system, it is a challenging task to continuously maintain optimal performance with a dynamic load profile. Coordination between the real-time controllers and system optimizer is not a trivial task in such conditions. Some of the protection schemes provide fault detection and isolation functions, but do not consider system level optimization constraints or power balance after fault isolation. In this paper, a novel methodology is introduced to control and optimally reconfigure a DC power system automatically detecting system disturbances. The proposed method includes autonomous fault detection and coordination of real-time constraint restricted problem formulation to optimize the system performance. A DC-bus distribution system developed for the U.S. Coast Guard's 270-ft Medium Endurance Cutter using Simulink's Simscape toolbox was used in this paper and bidirectional communication between the control and optimization system is implemented using CPLEX/MATLAB API. The simulation result demonstrates a successful performance over the scenarios considered.