Shishido Tânia K, Jokela Jouni, Fewer David P, Wahlsten Matti, Fiore Marli F, Sivonen Kaarina
Department of Food and Environmental Sciences, University of Helsinki , Viikki Biocenter 1, P.O. Box 56, 00014 Helsinki, Finland.
Center for Nuclear Energy in Agriculture, University of São Paulo , Avenida Centenário 303, Piracicaba, 13400-970, São Paulo, Brazil.
ACS Chem Biol. 2017 Nov 17;12(11):2746-2755. doi: 10.1021/acschembio.7b00570. Epub 2017 Sep 29.
Anabaenopeptins are a diverse group of cyclic peptides, which contain an unusual ureido linkage. Namalides are shorter structural homologues of anabaenopeptins, which also contain an ureido linkage. The biosynthetic origins of namalides are unknown despite a strong resemblance to anabaenopeptins. Here, we show the cyanobacterium Nostoc sp. CENA543 strain producing new (nostamide B-E (2, 4, 5, and 6)) and known variants of anabaenopeptins (schizopeptin 791 (1) and anabaenopeptin 807 (3)). Surprisingly, Nostoc sp. CENA543 also produced namalide B (8) and the new namalides D (7), E (9), and F (10) in similar amounts to anabaenopeptins. Analysis of the complete Nostoc sp. CENA543 genome sequence indicates that both anabaenopeptins and namalides are produced by the same biosynthetic pathway through module skipping during biosynthesis. This unique process involves the skipping of two modules present in different nonribosomal peptide synthetases during the namalide biosynthesis. This skipping is an efficient mechanism since both anabaenopeptins and namalides are synthesized in similar amounts by Nostoc sp. CENA543. Consequently, gene skipping may be used to increase and possibly broaden the chemical diversity of related peptides produced by a single biosynthetic gene cluster. Genome mining demonstrated that the anabaenopeptin gene clusters are widespread in cyanobacteria and can also be found in tectomicrobia bacteria.
鱼腥藻肽是一类多样的环肽,其含有一个不寻常的脲基连接。纳马肽是鱼腥藻肽的较短结构同源物,其也含有脲基连接。尽管纳马肽与鱼腥藻肽有很强的相似性,但其生物合成起源仍不清楚。在此,我们展示了蓝藻念珠藻属Nostoc sp. CENA543菌株产生新的(诺斯托酰胺B - E(2、4、5和6))以及已知的鱼腥藻肽变体(裂褶藻肽791(1)和鱼腥藻肽807(3))。令人惊讶的是,Nostoc sp. CENA543还产生了与鱼腥藻肽含量相似的纳马肽B(8)以及新的纳马肽D(7)、E(9)和F(10)。对Nostoc sp. CENA543完整基因组序列的分析表明,鱼腥藻肽和纳马肽是通过生物合成过程中的模块跳跃由相同的生物合成途径产生的。这一独特过程涉及在纳马肽生物合成过程中跳过存在于不同非核糖体肽合成酶中的两个模块。这种跳跃是一种有效的机制,因为Nostoc sp. CENA543合成的鱼腥藻肽和纳马肽含量相似。因此,基因跳跃可用于增加并可能拓宽由单个生物合成基因簇产生的相关肽的化学多样性。基因组挖掘表明,鱼腥藻肽基因簇在蓝藻中广泛存在,在微小杆菌中也能发现。