Rouhiainen Leo, Jokela Jouni, Fewer David P, Urmann Marina, Sivonen Kaarina
Department of Food and Environmental Sciences, P.O. Box 56, Viikki Biocenter, Viikinkaari 9, FIN-00014, University of Helsinki, Finland.
Chem Biol. 2010 Mar 26;17(3):265-73. doi: 10.1016/j.chembiol.2010.01.017.
Anabaenopeptins are a diverse family of cyclic hexapeptide protease inhibitors produced by cyanobacteria that contain a conserved ureido bond and D-Lys moiety. Here we demonstrate that anabaenopeptins are assembled on a nonribosomal peptide synthetase enzyme complex encoded by a 32 kb apt gene cluster in the cyanobacterium Anabaena sp. strain 90. Surprisingly, the gene cluster encoded two alternative starter modules organized in separate bimodular proteins. The starter modules display high substrate specificity for L-Arg/L-Lys and L-Tyr, respectively, and allow the specific biosynthesis of different anabaenopeptin variants. The two starter modules were found also in other Anabaena strains. However, just a single module was present in the anabaenopeptin gene clusters of Nostoc and Nodularia, respectively. The organization of the apt gene cluster in Anabaena represents an exception to the established colinearity rule of linear non-ribosomal peptide synthetases.
鱼腥藻肽是由蓝细菌产生的一类多样的环状六肽蛋白酶抑制剂，其含有一个保守的脲基键和D-赖氨酸部分。在此我们证明，鱼腥藻肽是在蓝细菌鱼腥藻菌株90中由一个32 kb的apt基因簇编码的非核糖体肽合成酶复合物上组装而成。令人惊讶的是，该基因簇编码了两个组织在不同双模块蛋白中的替代起始模块。起始模块分别对L-精氨酸/L-赖氨酸和L-酪氨酸表现出高底物特异性，并允许不同鱼腥藻肽变体的特异性生物合成。在其他鱼腥藻菌株中也发现了这两个起始模块。然而，念珠藻属和束毛藻属的鱼腥藻肽基因簇中分别仅存在一个模块。鱼腥藻中apt基因簇的组织代表了线性非核糖体肽合成酶既定共线性规则的一个例外。
