Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, Cambridge, UK.
Department of Structural and Functional Biology, Institute of Biology, UNICAMP, Campinas, SP, Brazil.
BMC Biotechnol. 2018 Apr 11;18(1):22. doi: 10.1186/s12896-018-0428-z.
Violacein is a deep violet compound that is produced by a number of bacterial species. It is synthesized from tryptophan by a pathway that involves the sequential action of 5 different enzymes (encoded by genes vioA to vioE). Violacein has antibacterial, antiparasitic, and antiviral activities, and also has the potential of inducing apoptosis in certain cancer cells.
Here, we describe the construction of a series of plasmids harboring the complete or partial violacein biosynthesis operon and their use to enable production of violacein and deoxyviolacein in E.coli. We performed in vitro assays to determine the biological activity of these compounds against Plasmodium, Trypanosoma, and mammalian cells. We found that, while deoxyviolacein has a lower activity against parasites than violacein, its toxicity to mammalian cells is insignificant compared to that of violacein.
We constructed E. coli strains capable of producing biologically active violacein and related compounds, and propose that deoxyviolacein might be a useful starting compound for the development of antiparasite drugs.
原标题:紫霉素是一种深紫色的化合物,由许多细菌种类产生。它是由色氨酸合成的,涉及 5 种不同酶(由 vioA 到 vioE 基因编码)的连续作用。紫霉素具有抗菌、抗寄生虫和抗病毒活性,并有诱导某些癌细胞凋亡的潜力。
在这里,我们描述了一系列质粒的构建,这些质粒含有完整或部分紫霉素生物合成操纵子,并用于在大肠杆菌中生产紫霉素和脱氧紫霉素。我们进行了体外测定,以确定这些化合物对疟原虫、锥虫和哺乳动物细胞的生物活性。我们发现,脱氧紫霉素对寄生虫的活性低于紫霉素,但与紫霉素相比,其对哺乳动物细胞的毒性微不足道。
我们构建了能够产生具有生物活性的紫霉素和相关化合物的大肠杆菌菌株,并提出脱氧紫霉素可能是开发抗寄生虫药物的有用起始化合物。