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Novel modifications of nonribosomal peptides from Brevibacillus laterosporus MG64 and investigation of their mode of action.
Applied and Environmental Microbiology ( IF 4.4 ) Pub Date : 2020-11-24 , DOI: 10.1128/aem.01981-20
Zhibo Li 1 , Reinder H de Vries 2 , Parichita Chakraborty 3 , Chunxu Song 4 , Xinghong Zhao 1 , Dirk-Jan Scheffers 3 , Gerard Roelfes 2 , Oscar P Kuipers 5
Affiliation  

Nonribosomal peptides (NRPs) are a class of secondary metabolites usually produced by microorganisms. They are of paramount importance in different applications, including biocontrol and pharmacy. Brevibacillus spp. are a rich source of NRPs yet have received little attention. In this study, we characterize four novel bogorol variants (bogorols I to L, cationic linear lipopeptides) and four succilins (succilins I to L, containing a succinyl group that is attached to the Orn3/Lys3 in bogorols I to L) from the biocontrol strain Brevibacillus laterosporus MG64. Further investigation revealed that the bogorol family of peptides employs an adenylation pathway for lipoinitiation, different from the usual pattern, which is based on an external ligase and coenzyme A. Moreover, the formation of valinol was proven to be mediated by a terminal reductase domain and a reductase encoded by the bogI gene. Furthermore, succinylation, which is a novel type of modification in the family of bogorols, was discovered. Its occurrence requires a high concentration of the substrate (bogorols), but its responsible enzyme remains unknown. Bogorols display potent activity against both Gram-positive and Gram-negative bacteria. Investigation of their mode of action reveals that bogorols form pores in the cell membrane of both Gram-positive and Gram-negative bacteria. The combination of bogorols and relacidines, another class of NRPs produced by B. laterosporus MG64, displays a synergistic effect on different pathogens, suggesting the great potential of both peptides as well as their producer B. laterosporus MG64 for broad applications. Our study provides a further understanding of the bogorol family of peptides as well as their applications.

中文翻译:

来自新孢子菌MG64的非核糖体肽的新型修饰及其作用方式的研究。

非核糖体肽(NRPs)是通常由微生物产生的一类次级代谢产物。它们在包括生物防治和药学在内的不同应用中至关重要。短杆菌属。是NRP的丰富来源,但很少受到关注。在这项研究中,我们表征了四个新的Bogorol变体(Bogorols I至L,阳离子线性脂肽)和四个Succilins(Succilins I至L,其含有连接至Bogorols I至L的Orn 3 / Lys 3的琥珀酰基)。生物控制菌株LaterosporusMG64。进一步的研究表明,bogorol肽家族采用不同于常规模式的腺苷酸化途径来进行脂肪起始,后者是基于外部连接酶和辅酶A的。此外,缬氨醇的形成被证明是由末端还原酶结构域和由bogI编码的还原酶基因。此外,发现丁二酸化是bogorols家族中的新型修饰类型。它的发生需要高浓度的底物(bogorols),但其负责的酶仍然未知。Bogorols对革兰氏阳性菌和革兰氏阴性菌均显示有效的活性。对它们的作用方式的研究表明,bogorols在革兰氏阳性细菌和革兰氏阴性细菌的细胞膜上均形成孔。Bogorols和relacidines的组合,由B. Laterosporus MG64生产的另一类NRP,对不同的病原体具有协同作用,表明这两种肽及其生产者B. Laterosporus都具有巨大潜力MG64适用于广泛的应用。我们的研究提供了进一步了解Bogorol肽家族及其应用。
更新日期:2020-11-25
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