Quinovosamycins: new tunicamycin-type antibiotics in which the α, β-1″,11′-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine
Quinovosamycins: new tunicamycin-type antibiotics in which the α, β-1″,11′-linked N-acetylglucosamine residue is replaced by N-acetylquinovosamine
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DOI：
10.1038/ja.2016.49
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发表时间：
2016-05
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通讯作者：
N. Price;D. Labeda;T. Naumann;Karl E. Vermillion;M. J. Bowman;M. Berhow;W. Metcalf;K. Bischoff
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作者：
N. Price;D. Labeda;T. Naumann;Karl E. Vermillion;M. J. Bowman;M. Berhow;W. Metcalf;K. Bischoff
衣霉素(Tun)是聚戊烯基磷酸N-乙酰己糖胺1-磷酸转移酶(PPHP)的有效抑制剂，包括真核细胞必需的GPT酶和细菌HexNAc 1-P转位酶。因此，Tun阻止了真核细胞N-糖蛋白的形成和细菌呼叫壁多糖的组装。对Tun生产的遗传要求是确定的。利用Tun途径特有的两个基因(TunB和TunD)作为探针，我们鉴定了四个新的Tun产生菌。化学分析表明，一株名为黑色链霉菌NRRL B-3857的菌株能产生Tun plus新化合物，称为喹诺沙星(QVMs)。QVm在结构上与Tun相似，但在1“，11‘-HexNAc糖头基团中是唯一的，对于已知Tun总是d-GlcNAc，但对于QVm是d-Quinac。令人惊讶的是，这种修饰对QVM和Tun的抑制或抗菌性能影响很小。这些发现对Tun/QVM的生物合成以及PPHP酶家族的特异性产生了意想不到的结果。
Tunicamycins (TUN) are potent inhibitors of polyprenyl phosphate N-acetylhexosamine 1-phosphate transferases (PPHP), including essential eukaryotic GPT enzymes and bacterial HexNAc 1-P translocases. Hence, TUN blocks the formation of eukaryotic N-glycoproteins and the assembly of bacterial call wall polysaccharides. The genetic requirement for TUN production is well-established. Using two genes unique to the TUN pathway (tunB and tunD) as probes we identified four new prospective TUN-producing strains. Chemical analysis showed that one strain, Streptomyces niger NRRL B-3857, produces TUN plus new compounds, named quinovosamycins (QVMs). QVMs are structurally akin to TUN, but uniquely in the 1 ″, 11′-HexNAc sugar head group, which is invariably d-GlcNAc for the known TUN, but is d-QuiNAc for the QVM. Surprisingly, this modification has only a minor effect on either the inhibitory or antimicrobial properties of QVM and TUN. These findings have unexpected consequences for TUN/QVM biosynthesis, and for the specificity of the PPHP enzyme family.