Heterologous production of new lanthipeptides hazakensins A and B using a cryptic gene cluster of the thermophilic bacterium Thermosporothrix hazakensis
Heterologous production of new lanthipeptides hazakensins A and B using a cryptic gene cluster of the thermophilic bacterium Thermosporothrix hazakensis
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利用嗜热细菌 Thermosporothrix hazakensis 的隐秘基因簇异源生产新的羊毛硫肽 hazakensins A 和 B
DOI：
10.1007/s11274-022-03463-6
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发表时间：
2022
影响因子：
4.1
通讯作者：
Kodani Shinya
中科院分区：
文献类型：
--
作者：
Kaweewan Issara;Ijichi Shinta;Nakagawa Hiroyuki;Kodani Shinya
嗜热菌Thermosporothrix hazakensis属于绿弯藻门中的一个类。羊毛硫肽是一种天然存在的肽类，含有抗菌化合物，如乳酸链球菌素。为了寻找一种新的羊毛硫肽作为抗菌剂的候选物，我们对T. hazakensi和异源表达实验。基于基因组挖掘，从T的基因组序列中，总共存在10个推定的I类和II类羊毛硫肽生物合成基因簇。通过在表达宿主大肠杆菌中异源表达I类羊毛硫肽生物合成基因簇，产生了新的羊毛硫肽，命名为hazakensins A和B。将该生物合成基因簇与T. hazakensis使两种羊毛硫肽的产率增加约4 - 6倍。通过NMR和MS实验确定了hazakensin A和B的化学结构，包括lanthioprene/methyllanthioprene环的桥接模式。由于在天然菌株T中未观察到哈扎菌素A和B的产生。异源生产是从生物合成基因簇中获得羊毛硫肽的有效方法。据我们所知，这是第一次从丝状绿色非硫细菌中异源生产I类羊毛硫肽的报道。异源生产哈扎菌素的成功可能会导致发现和开发新的lanthipeptides来源于Chloroflexota中的细菌来源。
The thermophilic bacteriumThermosporothrix hazakensisbelongs to a class ofKtedonobacteriain the phylumChloroflexota. Lanthipeptides are a naturally occurring peptide group that contains antibacterial compounds such as nisin. To find a new lanthipeptide that is a possible candidate for an antibacterial reagent, we performed genome-mining ofT. hazakensisand heterologous expression experiments. Based on genome-mining, the presence of a total of ten putative biosynthetic gene clusters for class I and class II lanthipeptides was indicated from the genome sequence ofT. hazakensis.New lanthipeptides named hazakensins A and B were produced by heterologous expression of a class I lanthipeptide biosynthetic gene cluster in the expression hostEscherichia coli. Co-expression of the biosynthetic gene cluster with tRNA-Glu and glutamyl-tRNA synthetase coding genes derived fromT. hazakensisincreased the production yield of both lanthipeptides by about 4–6 times. The chemical structures of hazakensins A and B including the bridging pattern of lanthionine/methyllanthionine rings were determined by NMR and MS experiments. Since production of hazakensins A and B was not observed in the native strainT. hazakensis, heterologous production was an effective method to obtain the lanthipeptides derived from the biosynthetic gene cluster. This is the first report of heterologous production of class I lanthipeptides originating from the filamentous green non-sulfur bacteria, to the best of our knowledge. The success of heterologous production of hazakensins may lead to the discovery and development of new lanthipeptides derived from the origins of bacteria in the phylumChloroflexota.
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来自极端微生物Thermogemmatispora T81菌株的一种新型羊毛硫肽（tikitericin）的基因组挖掘、分离、化学合成和生物学评估† †可获取电子补充信息（ESI）：10.1039/c8sc02170h。
影响因子：
8.4
作者：
Buzhe Xu;E. J. Aitken;Benjamin P. Baker;C. Turner;J. Harvey;M. Stott;J. F. Power;P. Harris;R. Keyzers;M. Brimble
通讯作者：
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影响因子：
15
作者：
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通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
Ovchinnikova, Tatiana V.
影响因子：
6.8
作者：
van der Donk, Wilfred A.;Nair, Satish K.
通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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