An orthogonal system for heterologous expression of actinobacterial lasso peptides in Streptomyces hosts

Scientific Reports
Jimmy MevaereYanyan Li

Abstract

Lasso peptides are ribosomally synthesized and post-translationally modified peptides produced by bacteria. They are characterized by an unusual lariat-knot structure. Targeted genome scanning revealed a wide diversity of lasso peptides encoded in actinobacterial genomes, but cloning and heterologous expression of these clusters turned out to be problematic. To circumvent this, we developed an orthogonal expression system for heterologous production of actinobacterial lasso peptides in Streptomyces hosts based on a newly-identified regulatory circuit from Actinoalloteichus fjordicus. Six lasso peptide gene clusters, mainly originating from marine Actinobacteria, were chosen for proof-of-concept studies. By varying the Streptomyces expression hosts and a small set of culture conditions, three new lasso peptides were successfully produced and characterized by tandem MS. The newly developed expression system thus sets the stage to uncover and bioengineer the chemo-diversity of actinobacterial lasso peptides. Moreover, our data provide some considerations for future bioprospecting efforts for such peptides.

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Citations

Jul 6, 2018·Chembiochem : a European Journal of Chemical Biology·Zhi FengTohru Dairi
Jan 9, 2019·Natural Product Reports·Liujie HuoRolf Müller
Jun 6, 2019·Journal of Industrial Microbiology & Biotechnology·Wai Ling Cheung-Lee, A James Link
Sep 17, 2020·Natural Product Reports·Manuel Montalbán-LópezWilfred A van der Donk
Jun 15, 2019·Natural Product Reports·Jia Jia ZhangBradley S Moore
Jul 25, 2020·Journal of Industrial Microbiology & Biotechnology·Shinya Kodani, Kohta Unno
Oct 30, 2020·Frontiers in Bioengineering and Biotechnology·Cheng Cheng, Zi-Chun Hua
Apr 7, 2021·Journal of the American Chemical Society·Yuanyuan SiDouglas A Mitchell
Jul 28, 2021·Journal of Agricultural and Food Chemistry·Yu LiWeisheng Cao
Sep 5, 2018·Journal of Natural Products·Helena Martin-GómezJulian D Hegemann
Dec 12, 2018·Journal of the American Chemical Society·Joseph D Koos, A James Link

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Datasets Mentioned

BETA
KX379996
KX379997
KX379998
KX379999
KX380000

Methods Mentioned

BETA
acetylation
PCR

Software Mentioned

Sci
antiSMASH
Clone Manager
Ed

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