With an emphasis on the class of cinnamyol, dihydrocinnamoyl, and benzoyl anthranilates, we illustrate in this study the possibility of producing numerous chemically diverse molecules using biological synthesis rather than conventional chemical synthesis. Our **data** imply that the promiscuity of 4CL5 allows the catalytic conversion of a great diversity of dihydrocinnamates, benzoates, and various cinnamates into the corresponding acyl-CoA-thioesters. To our doi:10.1371/journal.pone.0138972.g004 Table 3. Structural characteristics of the benzoyl anthranilates (general structure shown in Fig 1C) Table 3.  Our original attempts to co-express HCBT with known bacterial benzoyl:CoA ligases for the production of benzoyl anthranilates in yeast were unsuccessful, possibly due to the high pH optima (pH > 8.5) of these enzymes [36,37]. Nevertheless, using the 4CL5 enzyme, we demonstrate the feasibility of producing a substantial diversity of benzoyl-CoA thioesters and benzoate conjugate molecules in yeast. This discovery opens new possibilities for the heterologous combinatorial production of valuable benzoylated metabolites such as benzylbenzoates; benzophenones; the anticancer drug taxol; polyketides with antimicrobial activities (e.g., wailupemycin, enterocin, soraphen A); and unnatural polyketides using engineered benzoyl-CoAdependent polyketide synthases [38]. Furthermore, heterologously synthesized benzoyl anthranilates can be used as scaffolds for the synthesis of related anti-adenoviral compounds and oncogene inhibitors [39,40]. We observed the activity of 4CL5 towards various dihydrocinnamates and non-natural halogenated cinnamates and exploited its catalytic property to biosynthesize libraries of nonnatural and structurally diverse cinnamoyl and dihydrocinnamoyl anthranilates using HCBT. For example, the drug DHavnD was synthesized, and utilization of alternate precursors resulted in the rapid production of 27 additional DHavnD analogs. These results point towards the eventual design of more biologically active drugs through the addition of halogens. They also illustrate the advantage of biological synthesis to achieve bifunctionalization, as exemplified by several of our bi-halogenated compounds. Finally, through co-expression with the adequate synthases, the capacity of 4CL5 to activate dihydrocinnamates creates the potential for biomanufacture of valuable natural products, such as the antibacterial dihydrocinnamoyl forms of flavans and chalcones [41,42].