This paper presents the design and application of a fractional order asymptotic adaptive observer coupled to an adaptive controller for the robust operation of high-cell density cultures in fed-batch mode. The control goal is to maximize biomass productivity by controlling the culture's estimated specific growth rate. Since the specific growth rate cannot be measured, a fractional order asymptotic adaptive observer is proposed, based on the equivalent integer order asymptotic observer proposed before. Simulations are performed to validate the observer and controller, under the assumption that the system is in the oxidative regime under aerobic conditions. Obtained results show that, in close loop operation, the fractional adaptive observer behaves better than the integer order observer in the presence of measurement noise. For fractional orders of the observer in the range α G [0.6,0.8], it was observed a 51.71% increase in biomass concentration, compared to the biomass obtained with the classic integer-order observer. Furthermore, the controlled system reaches very low ethanol concentrations (< 1 grams per liter), which is desirable in this process.