Generation of structurally novel short carotenoids and study of their biological activity

Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C(30) carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C(30) carotenoids and one C(35) carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C(30) carotenoid structures revealed that acyclic C(30) carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C(30) carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C(30) carotenoid 4,4′-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli.