Autoinduction Specificities of the Lantibiotics Subtilin and Nisin

Autoinduction Specificities of the Lantibiotics Subtilin and Nisin
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羊毛硫抗生素枯草菌素和乳链菌肽的自诱导特性

DOI:
10.1128/aem.02392-15
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发表时间:
2015
影响因子:
4.4
通讯作者:
K.-D. Entian
K.-D. Entian
中科院分区:
生物学2区
文献类型:
--
作者:
T. Spieß;S. M. Korn;P. Kötter;K.-D. Entian

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羊毛硫抗生素枯草菌素和乳链菌肽的生物合成通过双组分系统通过自诱导进行调节。尽管枯草菌素在结构上与乳链菌肽密切相关并且含有相同的羊毛硫氨酸环结构,但这两种羊毛硫抗生素都特异性地自诱导其生物合成。枯草菌素以及类似枯草菌素的羊毛硫抗生素恩天宁和蓖麻毒素自诱导枯草芽孢杆菌的双组分系统SpaRK,而乳链菌肽的生物合成是通过乳酸乳球菌的双组分系统NisRK自诱导的。自诱导对于相应的羊毛硫抗生素具有高度特异性,因此对于基因工程枯草菌素样羊毛硫抗生素的功能表达具有重要意义。为了鉴定枯草菌素自诱导所需的结构特征,产生了枯草菌素-乳链菌肽杂合体和氨基酸位置1的特定点突变。对于枯草菌素自诱导,N 端色氨酸对于 SpaK 的完全激活最为重要。枯草菌素不能自诱导组氨酸激酶 NisK 主要取决于 N 末端色氨酸,因为其与脂肪族氨基酸残基异亮氨酸、亮氨酸和缬氨酸的单一交换提供了 NisK 自诱导。此外,在枯草芽孢杆菌DSM15029中异源共表达时,可以通过自诱导枯草菌素样羊毛硫抗生素安天宁来挽救不自诱导其自身生物合成的枯草菌素变体的产生。
The biosynthesis of the lantibiotics subtilin and nisin is regulated by autoinduction via two-component systems. Although subtilin is structurally closely related to nisin and contains the same lanthionine ring structure, both lantibiotics specifically autoinduce their biosynthesis. Subtilin and also the subtilin-like lantibiotics entianin and ericin autoinduce the two-component system SpaRK of Bacillus subtilis, whereas the biosynthesis of nisin is autoinduced via the two-component system NisRK of Lactococcus lactis. Autoinduction is highly specific for the respective lantibiotic and therefore of major importance for the functional expression of genetically engineered subtilin-like lantibiotics. To identify the structural features required for subtilin autoinduction, subtilin-nisin hybrids and specific point mutations of amino acid position 1 were generated. For subtilin autoinduction, the N-terminal tryptophan is the most important for full SpaK activation. The failure of subtilin to autoinduce the histidine kinase NisK mainly depends on the N-terminal tryptophan, as its single exchange to the aliphatic amino acid residues isoleucine, leucine, and valine provided NisK autoinduction. In addition, the production of subtilin variants which did not autoinduce their own biosynthesis could be rescued upon heterologous coexpression in B. subtilis DSM15029 by the autoinducing subtilin-like lantibiotic entianin.
组氨酸激酶 SpaK 的激活由枯草菌素样羊毛硫抗生素的 N 末端部分介导,且不依赖于脂质 II
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