14 CFR § 121.385

No certificate holder may operate an airplane with less than the minimum flight crew in the airworthiness certificate or the airplane Flight Manual approved for that type airplane and required by this part for the kind of operation being conducted.

In any case in which this part requires the performance of two or more functions for which an airman certificate is necessary, that requirement is not satisfied by the performance of multiple functions at the same time by one airman.

The minimum pilot crew is two pilots and the certificate holder shall designate one pilot as pilot in command and the other second in command.

On each flight requiring a flight engineer at least one flight crewmember, other than the flight engineer, must be qualified to provide emergency performance of the flight engineer's functions for the safe completion of the flight if the flight engineer becomes ill or is otherwise incapacitated. A pilot need not hold a flight engineer's certificate to perform the flight engineer's functions in such a situation.