Fewer David P, Wahlsten Matti, Österholm Julia, Jokela Jouni, Rouhiainen Leo, Kaasalainen Ulla, Rikkinen Jouko, Sivonen Kaarina
Division of Microbiology and Biotechnology, Department of Food and Environmental Sciences, University of Helsinki, Viikki Biocenter, P.O. Box 56, Viikinkaari 9, FIN-00014 Helsinki, Finland.
Chem Biol. 2013 Jul 25;20(7):861-9. doi: 10.1016/j.chembiol.2013.04.020.
Microcystins are a family of cyclic peptide toxins produced by cyanobacteria. They are responsible for the toxicosis and death of wild and domestic animals throughout the world. They display extensive variation in amino acid composition and functional group chemistry. O-acetylated microcystins are frequently produced by free-living and symbiotic strains of the genus Nostoc. Here, we show that the production of acetylated microcystins is catalyzed by an acetyl-coenzyme A-dependent O-acetyltransferase (McyL) encoded in the 57 kb microcystin synthetase gene cluster of Nostoc sp. 152. Phylogenetic analysis demonstrates that McyL belongs to a family of enzymes that inactivate antibiotics through O-acetylation. The McyL enzyme has a relaxed substrate specificity, allowing the preparation of semisynthetic microcystins. This study sheds light on the evolutionary origins and genetic diversity of an important class of enzymes involved in antibiotic resistance.
微囊藻毒素是一类由蓝细菌产生的环状肽毒素。它们导致了世界各地野生动物和家畜的中毒和死亡。它们在氨基酸组成和官能团化学方面表现出广泛的差异。O-乙酰化微囊藻毒素通常由念珠藻属的自由生活和共生菌株产生。在此，我们表明乙酰化微囊藻毒素的产生是由念珠藻属152株5７kb微囊藻毒素合成酶基因簇中编码的一种依赖乙酰辅酶A的O-乙酰转移酶（McyL）催化的。系统发育分析表明，McyL属于一类通过O-乙酰化使抗生素失活的酶家族。McyL酶具有宽松的底物特异性，这使得半合成微囊藻毒素的制备成为可能。这项研究揭示了一类参与抗生素抗性的重要酶的进化起源和遗传多样性。
