The invention concerns novel isolated natural or synthetic polynucleotides and polypeptides coded by said polynucleotides, involved in the synthesis of diketopiperazine derivatives, vectors comprising said polynucleotides, micro-organisms transformed with said polynucleotides, uses of said polynucleotides and said polypeptides, as well as methods for the synthesis of diketopiperazine derivatives, including cyclodipeptides and diketopiperazine derivatives 3- and 6- substituted by .alpha.,.beta.-unsaturated amino acid side chains.