干旱区生态环境知识资源中心(Arid): Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34(T) Yields a Novel Lasso Peptide, Leepeptin

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DOI	10.1128/AEM.01752-19
	Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34(T) Yields a Novel Lasso Peptide, Leepeptin
	Gomez-Escribano, Juan Pablo 1; Castro, Jean Franco 1,2,3; Razmilic, Valeria 1,2; Jarmusch, Scott A.3; Saalbach, Gerhard 1; Ebel, Rainer 3; Jaspars, Marcel 3; Andrews, Barbara 2; Asenjo, Juan A.2; Bibb, Mervyn J.1
通讯作者	Bibb, Mervyn J.
来源期刊	APPLIED AND ENVIRONMENTAL MICROBIOLOGY
ISSN	0099-2240
EISSN	1098-5336
出版年	2019
卷号	85 期号:23
英文摘要	Analysis of the genome sequence of Streptomyces leeuwenhoekii C34(T) identified biosynthetic gene clusters (BGCs) for three different lasso peptides (Lp1, Lp2, and Lp3) which were not known to be made by the strain. Lasso peptides represent relatively new members of the RiPP (ribosomally synthesized and posttranslationally modified peptides) family of natural products and have not been extensively studied. Lp3, whose production could be detected in culture supernatants from S. leeuwenhoekii C34(T) and after heterologous expression of its BGC in Streptomyces coelicolor, is identical to the previously characterized chaxapeptin. Lp1, whose production could not be detected or achieved heterologously, appears to be identical to a recently identified member of the citrulassin family of lasso peptides. Since production of Lp2 by S. leeuwenhoekii C34(T) was not observed, its BGC was also expressed in S. coelicolor. The lasso peptide was isolated and its structure confirmed by mass spectrometry and nuclear magnetic resonance analyses, revealing a novel structure that appears to represent a new family of lasso peptides. IMPORTANCE Recent developments in genome sequencing combined with bioinformatic analysis have revealed that actinomycetes contain a plethora of unexpected BGCs and thus have the potential to produce many more natural products than previously thought. This reflects the inability to detect the production of these compounds under laboratory conditions, perhaps through the use of inappropriate growth media or the absence of the environmental cues required to elicit expression of the corresponding BGCs. One approach to overcoming this problem is to circumvent the regulatory mechanisms that control expression of the BGC in its natural host by deploying heterologous expression. The generally compact nature of lasso peptide BGCs makes them particularly amenable to this approach, and, in the example given here, analysis revealed a new member of the lasso peptide family of RIPPs. This approach should be readily applicable to other cryptic lasso peptide gene clusters and would also facilitate the design and production of nonnatural variants by changing the sequence encoding the core peptide, as has been achieved with other classes of RIPPs.
英文关键词	Streptomyces natural products RiPP lasso peptide heterologous expression
类型	Article
语种	英语
国家	England ; Chile ; Scotland
开放获取类型	Green Published, hybrid
收录类别	SCI-E
WOS记录号	WOS:000499131000016
WOS关键词	BIOSYNTHESIS ; RESTRICTION ; CHAXAMYCINS ; COELICOLOR ; RESISTANCE ; SEQUENCE ; BINDING ; DESERT ; TOOL
WOS类目	Biotechnology & Applied Microbiology ; Microbiology
WOS研究方向	Biotechnology & Applied Microbiology ; Microbiology
EI主题词	2019-12-01
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/311240
作者单位	1.John Innes Ctr, Dept Mol Microbiol, Norwich, Norfolk, England; 2.Univ Chile, Ctr Biotechnol & Bioengn CeBiB, Dept Chem Engn & Biotechnol, Santiago, Chile; 3.Univ Aberdeen, Marine Biodiscovery Ctr, Dept Chem, Old Aberdeen, Scotland
推荐引用方式 GB/T 7714	Gomez-Escribano, Juan Pablo,Castro, Jean Franco,Razmilic, Valeria,et al. Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34(T) Yields a Novel Lasso Peptide, Leepeptin[J],2019,85(23).
APA	Gomez-Escribano, Juan Pablo.,Castro, Jean Franco.,Razmilic, Valeria.,Jarmusch, Scott A..,Saalbach, Gerhard.,...&Bibb, Mervyn J..(2019).Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34(T) Yields a Novel Lasso Peptide, Leepeptin.APPLIED AND ENVIRONMENTAL MICROBIOLOGY,85(23).
MLA	Gomez-Escribano, Juan Pablo,et al."Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34(T) Yields a Novel Lasso Peptide, Leepeptin".APPLIED AND ENVIRONMENTAL MICROBIOLOGY 85.23(2019).