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新型环缩酚酸肽类抗生素的发现及异源生产

Discovery and Heterologous Production of New Cyclic Depsibosamycins.

作者信息

Stierhof Marc, Myronovskyi Maksym, Zapp Josef, Luzhetskyy Andriy

机构信息

Department of Pharmaceutical Biotechnology, Saarland University, 66123 Saarbruecken, Germany.

Department of Pharmaceutical Biology, Saarland University, 66123 Saarbruecken, Germany.

出版信息

Microorganisms. 2021 Jun 28;9(7):1396. doi: 10.3390/microorganisms9071396.

DOI:10.3390/microorganisms9071396
PMID:34203385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8303602/
Abstract

are producers of valuable secondary metabolites with unique scaffolds that perform a plethora of biological functions. Nonribosomal peptides are of special interest due to their variety and complexity. They are synthesized by nonribosomal peptide synthetases, large biosynthetic machineries that are encoded in the genome of many species. The identification of new peptides and the corresponding biosynthetic gene clusters is of major interest since knowledge can be used to facilitate combinatorial biosynthesis and chemical semisynthesis of natural products. The recently discovered bosamycins are linear octapeptides with an interesting 5-OMe tyrosine moiety and various modifications at the -terminus. In this study, the new cyclic depsibosamycins B, C, and D from LU19075 were discovered. In comparison to the linear bosamycins B, C, and D, which were also produced by the strain, the cyclic depsibosamycins showed a side-chain-to-tail lactonization of serine and glycine, leading to a ring of four amino acids. In silico identification and heterologous expression of the depsibosamycin () gene cluster indicated that the cyclic peptides, rather than the linear derivatives, are the main products of the cluster.

摘要

是具有独特支架结构的有价值次生代谢产物的生产者,这些次生代谢产物具有众多生物学功能。非核糖体肽因其多样性和复杂性而备受关注。它们由非核糖体肽合成酶合成,非核糖体肽合成酶是许多物种基因组中编码的大型生物合成机制。鉴定新的肽及其相应的生物合成基因簇具有重要意义,因为相关知识可用于促进天然产物的组合生物合成和化学半合成。最近发现的博萨霉素是具有有趣的5-甲氧基酪氨酸部分且在C末端有各种修饰的线性八肽。在本研究中,从LU19075中发现了新的环缩酚酸肽博萨霉素B、C和D。与该菌株产生的线性博萨霉素B、C和D相比,环缩酚酸肽博萨霉素显示出丝氨酸和甘氨酸的侧链到尾端内酯化,形成了一个由四个氨基酸组成的环。环缩酚酸肽博萨霉素()基因簇的计算机鉴定和异源表达表明,环肽而非线性衍生物是该基因簇的主要产物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/cb83117af206/microorganisms-09-01396-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/9d596eb07534/microorganisms-09-01396-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/1ead43449499/microorganisms-09-01396-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/f8daafc9d646/microorganisms-09-01396-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/ff27d8c78291/microorganisms-09-01396-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/cb83117af206/microorganisms-09-01396-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/9d596eb07534/microorganisms-09-01396-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/1ead43449499/microorganisms-09-01396-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/f8daafc9d646/microorganisms-09-01396-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/ff27d8c78291/microorganisms-09-01396-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b49/8303602/cb83117af206/microorganisms-09-01396-g005.jpg

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