The mycosubtilin synthetase of Bacillus subtilis ATCC6633:: A multifunctional hybrid between a peptide synthetase, an amino transferase, and a fatty acid synthase
The mycosubtilin synthetase of Bacillus subtilis ATCC6633:: A multifunctional hybrid between a peptide synthetase, an amino transferase, and a fatty acid synthase
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DOI：
10.1073/pnas.96.23.13294
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发表时间：
1999-11-09
影响因子：
11.1
通讯作者：
Vater, J
中科院分区：
文献类型：
--
作者：
Duitman, EH;Hamoen, LW;Vater, J
枯草芽孢杆菌菌株ATCC 6633已被鉴定为产生真菌枯草菌素，一种有效的抗真菌肽抗生素。菌枯草菌素属于伊枯草菌素脂肽抗生素家族，其特征在于与环状七肽Asn-Tyr-Asn-Cln-Pro-Ser-Asn连接的β-氨基脂肪酸部分，其中第二、第三和第六位以D-构型存在。来自B的基因簇。鉴定了指定真菌枯草菌素生物合成的sobacillus ATCC 6633。推定的操纵子跨度38 kb，由四个ORF组成，命名为fenF，mycA，mycB和mycC，与肽合成酶家族具有很强的同源性。生物化学表征表明，MycB特异性腺苷酪氨酸，如预期的菌枯草菌素合成酶，和插入诱变的操纵子导致菌枯草菌素阴性表型。真菌枯草菌素合成酶显示肽合成酶以及脂肪酸脱氢酶独特的特征：（i）真菌枯草菌素合成酶亚基A（MycA）结合了源自肽合成酶的功能结构域。氨基转移酶和脂肪酸脱氢酶。MycA代表了这些酶家族之间天然杂交的第一个例子。(ii)合成酶亚基的结构不同于肽合成酶中常见的结构。根据所描述的枯草菌素合成酶的特性，我们提出了一个伊枯草菌素脂肽类抗生素生物合成的模型。B的菌枯草菌素操纵子侧翼序列的比较。sobacillusATCC 6633的全基因组序列，并与B的全基因组序列进行比较。sobacillus菌株168表明芬枯草菌素和枯草菌素脂肽合成酶操纵子在两个B之间交换。sobobbestry应变。
Bacillus subtilis strain ATCC6633 has been identified as a producer of mycosubtilin, a potent antifungal peptide antibiotic. Mycosubtilin, which belongs to the iturin family of lipopeptide antibiotics, is characterized by a p-amino fatty acid moiety linked to the circular heptapeptide Asn-Tyr-Asn-Cln-Pro-Ser-Asn, with the second, third, and sixth position present in the D-configuration. The gene cluster from B. sobtilis ATCC6633 specifying the biosynthesis of mycosubtilin was identified. The putative operon spans 38 kb and consists of four ORFs, designated fenF, mycA, mycB, and mycC, with strong homologies to the family of peptide synthetases. Biochemical characterization showed that MycB specifically adenylates tyrosine, as expected for mycosubtilin synthetase, and insertional mutagenesis of the operon resulted in a mycosubtilin-negative phenotype. The mycosubtilin synthetase reveals features unique for peptide synthetases as well as for fatty acid synthases: (i) The mycosubtilin synthase subunit A (MycA) combines functional domains derived from peptide synthetases. amino transferases, and fatty acid synthases. MycA represents the first example of a natural hybrid between these enzyme families. (ii) The organization of the synthetase subunits deviates from that commonly found in peptide synthetases. On the basis of the described characteristics of the mycosubtilin synthetase, we present a model for the biosynthesis of iturin lipopeptide antibiotics. Comparison of the sequences flanking the mycosubtilin operon of B. sobtilis ATCC6633, with the complete genome sequence of B. sobtilis strain 168 indicates that the fengycin and mycosubtilin lipopeptide synthetase operons are exchanged between the two B. sobtilis strains.