Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator

Sánchez‐Hidalgo, Marina; Martín, Jesús; Genilloud, Olga

doi:10.3390/antibiotics9020067

Cited by 19 publications

(21 citation statements)

References 41 publications

(68 reference statements)

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“…Humidimycin was characterized as a new synergist of the fungal cell wall biosynthesis inhibitor caspofungin (Valiante et al, 2015). The lack of cytotoxicity of humidimycin alone suggests its possible use as a combined treatment of invasive fungal infections (Valiante et al, 2015;Sanchez-Hidalgo et al, 2020). Based on the assessment of PEP levels in the postmortem brain of patients with Alzheimer's disease, a strong correlation was established between the increase in PEP activity and Alzheimer's disease (Aoyagi et al, 1990).…”

Section: Potential Application Of Lasso Peptides Therapeutical Potentmentioning

confidence: 99%

“…K01-B0171 exhibited selective activity against M. smegmatis (MICs of 3.13–6.25 μg/mL; DIZs of 18–19 mm at 10 μg/disk). Additionally, humidimycin identified from Streptomyces humidus CA-100629 was characterized as an anti-fungal enhancer of the fungal cell wall inhibitor caspofungin against Candida albicans and Aspergillus fumigatus , and itraconazole against A. fumigatus ( Valiante et al, 2015 ; Sanchez-Hidalgo et al, 2020 ). It is suggested that the synergistic effect exerted by the drug combination results from the misbalancing of the high osmolarity glycerol signaling pathway and hitting the caspofungin salvage pathway of human-pathogenic fungi.…”

Section: Bioactivities Of Lasso Peptidesmentioning

confidence: 99%

“…It was observed in previous studies that lasso peptides possess antiviral effects ( Table 3 ). The siamycin-type lasso peptides from Streptomyces like siamycin I (MS-271, BMY29304)/II (BMY 29303) ( Constantine et al, 1995 ; Tsunakawa et al, 1995 ; Yano et al, 1996 ), aborycin/RP 71955 ( Potterat et al, 1994 ), humidimycin ( Valiante et al, 2015 ; Sanchez-Hidalgo et al, 2020 ), specialicin ( Kaweewan et al, 2018 ) are most frequently described. They differ from one another only at position 4 (Val or Ile), 8 (Asp, Asn, and Val) or17 (Val or Ile).…”

Section: Bioactivities Of Lasso Peptidesmentioning

confidence: 99%

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Lasso Peptides: Heterologous Production and Potential Medical Application

Cheng

Hua

2020

Front. Bioeng. Biotechnol.

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Lasso peptides are natural products found in bacteria. They belong to a specific family of ribosomally-synthesized and posttranslationally-modified peptides with an unusual lasso structure. Lasso peptides possess remarkable thermal and proteolytic stability and various biological activities, such as antimicrobial activity, enzyme inhibition, receptor blocking, anticancer properties and HIV antagonism. They have promising potential therapeutic effects on gastrointestinal diseases, tuberculosis, Alzheimer's disease, cardiovascular disease, fungal infections and cancer. Lasso peptides with high stability have been shown to be good carriers for other bioactive peptides. These make them attractive candidates for pharmaceutical research. This review aimed to describe the strategies used for the heterologous production of lasso peptides. Also, it indicated their therapeutical potential and their capacity to use as an efficient scaffold for epitope grafting.

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Section: Potential Application Of Lasso Peptides Therapeutical Potentmentioning

confidence: 99%

Section: Bioactivities Of Lasso Peptidesmentioning

confidence: 99%

Section: Bioactivities Of Lasso Peptidesmentioning

confidence: 99%

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Lasso Peptides: Heterologous Production and Potential Medical Application

Cheng

Hua

2020

Front. Bioeng. Biotechnol.

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“…In recent years, two new anti-HIV class I lasso peptides, i.e., specialicin (active against HIV-1 NL4-3 with IC 50 around 7.2 µM) [ 48 ] and humidimycin [ 58 ] were identified based on genome mining, then isolated and characterized. The structural elucidation showed that they are closely related to siamycins, possessing anti-HIV activity with no significant toxicity.…”

Section: Introductionmentioning

confidence: 99%

Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs)

Jaarsma

Kuipers

2021

Cell. Mol. Life Sci.

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The emergence and re-emergence of viral epidemics and the risks of antiviral drug resistance are a serious threat to global public health. New options to supplement or replace currently used drugs for antiviral therapy are urgently needed. The research in the field of ribosomally synthesized and post-translationally modified peptides (RiPPs) has been booming in the last few decades, in particular in view of their strong antimicrobial activities and high stability. The RiPPs with antiviral activity, especially those against enveloped viruses, are now also gaining more interest. RiPPs have a number of advantages over small molecule drugs in terms of specificity and affinity for targets, and over protein-based drugs in terms of cellular penetrability, stability and size. Moreover, the great engineering potential of RiPPs provides an efficient way to optimize them as potent antiviral drugs candidates. These intrinsic advantages underscore the good therapeutic prospects of RiPPs in viral treatment. With the aim to highlight the underrated antiviral potential of RiPPs and explore their development as antiviral drugs, we review the current literature describing the antiviral activities and mechanisms of action of RiPPs, discussing the ongoing efforts to improve their antiviral potential and demonstrate their suitability as antiviral therapeutics. We propose that antiviral RiPPs may overcome the limits of peptide-based antiviral therapy, providing an innovative option for the treatment of viral disease.

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“…A recent report by the World Health Organization (WHO) highlights the need to explore novel chemistry from nature amid the increasing problems caused by antimicrobial-resistant (AMR) bacteria [5]. It was previously estimated that there might be billions of microbial species living on earth [6,7] and even from the heavily mined genus of Streptomyces, novel discoveries continue to be made [8][9][10][11][12][13]. Due to the sheer size of microbial and enzymological biodiversity, there exists a vast repertoire of potentially useful compounds remains to be unearthed.…”

Section: Introductionmentioning

confidence: 99%

BiG-SLiCE: A Highly Scalable Tool Maps the Diversity of 1.2 Million Biosynthetic Gene Clusters

Kautsar

Hooft

Ridder

et al. 2020

Preprint

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Genome mining for Biosynthetic Gene Clusters (BGCs) has become an integral part of natural product discovery. The >200,000 microbial genomes now publicly available hold information on abundant novel chemistry. One way to navigate this vast genomic diversity is through comparative analysis of homologous BGCs, which allows identification of cross-species patterns that can be matched to the presence of metabolites or biological activities. However, current tools suffer from a bottleneck caused by the expensive network-based approach used to group these BGCs into Gene Cluster Families (GCFs). Here, we introduce BiG-SLiCE, a tool designed to cluster massive numbers of BGCs. By representing them in Euclidean space, BiG-SLiCE can group BGCs into GCFs in a non-pairwise, near-linear fashion. We used BiG-SLiCE to analyze 1,225,071 BGCs collected from 209,206 publicly available microbial genomes and metagenome-assembled genomes (MAGs) within ten days on a typical 36-cores CPU server. We demonstrate the utility of such analyses by reconstructing a global map of secondary metabolic diversity across taxonomy to identify uncharted biosynthetic potential. BiG-SLiCE also provides a "query mode" that can efficiently place newly sequenced BGCs into previously computed GCFs, plus a powerful output visualization engine that facilitates user-friendly data exploration. BiG-SLiCE opens up new possibilities to accelerate natural product discovery and offers a first step towards constructing a global, searchable interconnected network of BGCs. As more genomes get sequenced from understudied taxa, more information can be mined to highlight their potentially novel chemistry. BiG-SLiCE is available via https://github.com/medema-lab/bigslice.

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Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator

Cited by 19 publications

References 41 publications

Lasso Peptides: Heterologous Production and Potential Medical Application

Lasso Peptides: Heterologous Production and Potential Medical Application

Antiviral activities and applications of ribosomally synthesized and post-translationally modified peptides (RiPPs)

BiG-SLiCE: A Highly Scalable Tool Maps the Diversity of 1.2 Million Biosynthetic Gene Clusters

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