An Overview of Brevinin Superfamily : Structure, Function and Clinical Perspectives

Antimicrobial peptides are the backbone of first-line defense againstvarious microorganisms in the animal kingdom. Thus, not surprisingly, they aregaining attention in the science and medical fields as a rich repository of newpro-drugs. Below, we focus our attention on the Brevinin family of anuran peptides.While most of them show strong antibacterial activities, some, e.g. Brevinin-2R,appear to be promising anticancer molecules, exhibiting better a therapeutic windowthan widely-use anticancer drugs like doxorubicin. We briefly introduce thefield, followed by highlighting the promising therapeutic properties of Brevinins.Next, we provide information about the cloning and phylogenetic aspects ofBrevinin genes. In the final paragraphs of this chapter, we discuss possible largescaleproduction methods of Brevinins, giving examples of some systems that arealready in use. Towards the end, we discuss various means of modification ofbiologic properties of Brevinins, either by chemical modifications or by aminoacid substitution and sequence rearrangements. In this context, also other uniqueproperties of Brevinins are briefly mentioned. Finally, we discuss the future of theBrevinin field, particularly highlighting yet to be answered biologic questions, likefor example presumed anti-viral and antitumor activities of Brevinin familymembers.PMID: 25001538</p

Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis

Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis