Expression and Subcellular Localization of Lanthipeptides in Human Cells DOI Creative Commons
Sara M. Eslami, Chandrashekhar Padhi, Imran R. Rahman

et al.

ACS Synthetic Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 2128 - 2140

Published: June 26, 2024

Cyclic peptides, such as most ribosomally synthesized and post-translationally modified peptides (RiPPs), represent a burgeoning area of interest in therapeutic biotechnological research because their conformational constraints reduced susceptibility to proteolytic degradation compared linear counterparts. Herein, an expression system is reported that enables the production structurally diverse lanthipeptides derivatives mammalian cells. Successful targeting nucleus, endoplasmic reticulum, plasma membrane demonstrated. In vivo cells may allow for screening lanthipeptide-based cyclic peptide inhibitors native, organelle-specific protein–protein interactions systems.

Language: Английский

Transformation-Guided Genome Mining Provides Access to Brominated Lanthipeptides DOI Creative Commons
Nirmal Saha,

F. N. U. Vidya,

Youran Luo

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: 27(4), P. 984 - 988

Published: Jan. 17, 2025

Natural product biosynthesis is nature's tinkering ground for developing new enzymes that can achieve chemical transformations are outside the purview of traditional catalysis. Herein we describe a genome mining approach leads to discovery halogenase regioselectively brominates tryptophan side chain indole macrocyclic peptide substrate, enabling downstream arylation by Suzuki-Miyaura coupling. The was found prefer substrate over linear peptide. brominase presents starting point biocatalytic access peptides bearing chemically versatile aryl-bromide reactive handle.

Language: Английский

Citations

4
Deciphering the chemical landscape and potential ecological function of RiPPs from the untapped Archaea domain DOI Open Access

Zhi‐Man Song,

Cunlei Cai,

Ying Gao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 8, 2024

Abstract Chemical communication is crucial in ecosystems with complex microbial communities. However, the difficulties inherent to cultivation of archaea have led a limited understanding their chemical language, especially regarding structure diversity and function secondary or specialized metabolites (SMs). Our comprehensive investigation into biosynthetic potential archaea, combined metabolic analyses first report heterologous expression has unveiled previously unexplored capabilities archaeal ribosomally synthesized post-translationally modified peptides (RiPPs). We identified twenty-four new lanthipeptides RiPPs exhibiting unique characteristics, including novel subfamily featuring an type diamino-dicarboxylic (DADC) termini, largely expanding landscape SMs. This sheds light on novelty emphasizes as untapped resource for natural product discovery. Additionally, demonstrate specific antagonistic activity against haloarchaea, mediating biotic interaction halophilic niche. Furthermore, they showcase ecological role enhancing host’s motility by inducing rod-shaped cell morphology upregulating archaellin gene expression, facilitating abiotic environments. These discoveries broaden our language provide promising prospects future exploration SM-mediated interaction. Figure

Language: Английский

Citations

1
Initial Characterization of the Viridisins’ Biological Properties DOI Creative Commons
Ross Rayne Vermeulen, Anton D. van Staden, Tracey Ollewagen

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(29), P. 31832 - 31841

Published: July 9, 2024

Viridisin A1 and A2 were previously heterologously expressed, purified, characterized as ribosomally produced post-translationally modified lanthipeptides. Such lanthipeptide operons are surprisingly common in Gram-negative bacteria, although their expression seems to be predominantly cryptic under laboratory conditions. However, the bioactivity biological role of most originating from marine-associated Pseudomonadota, such asThalassomonas viridans XOM25T, have not been described. Therefore, represent an untapped resource for novel structures, biochemistries, bioactivities. Here, upscaled production viridisin was performed (methyl)lanthionine stereochemistry characterization, antibacterial, antifungal, larval zebrafish behavioral screening. While antimicrobial activity observed, VirBC modification machinery found install both dl- ll-lanthionine stereoisomers. The VdsA1 VdsA2 peptides induced sedative stimulatory effects larvae, respectively, which is a reported When combined, counteracted observed when used individually.

Language: Английский

Citations

0
Bibacillin 1: A two-component lantibiotic fromBacillus thuringiensis DOI Creative Commons
Ryan Moreira,

Yi Yang,

Youran Luo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

Abstract Here we describe bibacillin 1 – a two-component lantibiotic from Bacillus thuringiensis . The peptides that comprise are modified by class II lanthipeptide synthetase Bib1M producing two with non-overlapping ring patterns reminiscent of cerecidin and the short component enterococcal cytolysin (CylLS”), virulence factor associated human disease. Stereochemical analysis demonstrated each contains LL-methyllanthionine DL-lanthionine. mature showed cooperative bactericidal activity against Gram-positive bacteria, including members ESKAPE pathogens, weak hemolytic activity. Optimal ratio studies suggest works best when components present in 1:1 ratio, but near optimal was observed at ratios strongly favouring one over other, suggesting may have different complementary targets. Mechanism action lipid II-independent killing distinguishing other lantibiotics haloduracin lacticin 3147. One cross reactivity regulatory system. These result support involvement quorum sensing raise questions about impact CylL S ”-like natural products on expression diverse bacterial communities.

Language: Английский

Citations

0
Bibacillin 1: A two-component lantibiotic from Bacillus thuringiensis DOI Creative Commons
Ryan Moreira,

Yi Yang,

Youran Luo

et al.

RSC Chemical Biology, Journal Year: 2024, Volume and Issue: 5(10), P. 1060 - 1073

Published: Jan. 1, 2024

Here we describe the structure, bioactivity, and action mechanism of bibacillin 1 – a two-component lantibiotic from Bacillus thuringiensis.

Language: Английский

Citations

0
Expression and Subcellular Localization of Lanthipeptides in Human Cells DOI Creative Commons
Sara M. Eslami, Chandrashekhar Padhi, Imran R. Rahman

et al.

ACS Synthetic Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 2128 - 2140

Published: June 26, 2024

Cyclic peptides, such as most ribosomally synthesized and post-translationally modified peptides (RiPPs), represent a burgeoning area of interest in therapeutic biotechnological research because their conformational constraints reduced susceptibility to proteolytic degradation compared linear counterparts. Herein, an expression system is reported that enables the production structurally diverse lanthipeptides derivatives mammalian cells. Successful targeting nucleus, endoplasmic reticulum, plasma membrane demonstrated. In vivo cells may allow for screening lanthipeptide-based cyclic peptide inhibitors native, organelle-specific protein–protein interactions systems.

Language: Английский

Citations

0