Group contribution methods are suitable tools for estimating many physicochemical properties of pure compounds and mixtures. The classical group contribution method decomposes each chemical compound into first, second, and third-order functional groups based on its molecular structure. The most significant advantage of these methods is that they need only the compounds chemical structure without any other input information. From these approaches, structural fragments and subsequent group contribution methods can be established. The knowledge of the molecular structure and its decomposing into molecular fragments can optimize the production of biosynthesis compounds for chemical and pharmaceutical industries. The current research proposes an innovative group contribution application as selection criteria to culture media carbon and nitrogen sources. The concept is based on group contribution to identifying molecular fragments present in tacrolimus structure. Tacrolimus is a macrolide lactone originally obtained from fermentation of Streptomyces tsukubaensis broth. This drug decreases the occurrence and severity of refractory rejection episodes. In addition, tacrolimus is recommended for the treatment of autoimmune diseases. In order to investigate the application of the group contribution, tacrolimus molecular structure and fermentation results of this macrolide were analyzed. This approach can enhance productivity of this important immunosuppressant.