Correction to: Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens

Iacovelli, Riccardo; Bovenberg, Roel A. L.; Driessen, Arnold J.M.

doi:10.1093/jimb/kuac005

Cited by 5 publications

(6 citation statements)

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“…The review by Iacovelli et al . 82 reports 33 essential biosynthetic genes encoding 10 non-ribosomal peptides synthetases (NRPSs), 20 polyketide synthetases (PKSs), 2 hybrid NRPS-PKSs, and 1 dimethyl-allyl-tryptophan synthetase (DMATS). Among the non-ribosomal peptides identified, we find fungisporin, roquefortine C, D, F, M, and N, as well as associated products such as meleagrin, glandicolins A and B, histidyltryptophanyldi-ketopiperazine (HTD) and dehydrohistidyltryptophanyldiketopiperazine (DHTD).…”

Section: Discussionmentioning

confidence: 99%

Reconciliation and evolution ofPenicillium rubensGenome-Scale Metabolic Networks – What about specialised metabolism?

Nègre

Larhlimi

Bertrand

2022

Preprint

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Mining filamentous fungal genomes have revealed a high proportion of specialised metabolites in the past few years. However, many of these metabolites, produced by biosynthetic gene clusters, remain silent in the laboratory and one hypothesis for soliciting their production lies in modifying their growth conditions. Though, it remains a time-consuming and costly process. Therefore, the preliminary use of in silico modelling, such Genome Scale Metabolic Network (GSMN), might be a clever alternative to explore and understand the production potential of a given organism. Consequently, Penicillium rubens Wisconsin 54-1255 strain was selected as the model organism. Following current convention standards and quality criteria, the proposed reconstruction results from the following four elements. In parallel, (1) an updated functional annotation of the P. rubens genome was carried out and supplemented by (2) an orthology search with different GSMNs templates. This first draft was enriched (3) by integrating data from P. rubens previous GSMN reconstructions and complemented (4) by manual curation steps targeting basal and specialised metabolites. The proposed high-quality GSMN, iPrub22, has a MEMOTE score of 68% and a metabolic coverage of 45%. The reconstruction is composed of 5,192 metabolites interconnected by 5,897 reactions, of which 5,033 are at least supported by a genomic sequence. In fine, the presence within iPrub22 of the specialised metabolisms highlights that many bottlenecks still exist. Solving such problems is the mandatory step to get access to specialised metabolic dedicated GSMN suitable for the exploration of metabolic regulation responsible for natural product synthesis.

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Section: Discussionmentioning

confidence: 99%

Reconciliation and evolution ofPenicillium rubensGenome-Scale Metabolic Networks – What about specialised metabolism?

Nègre

Larhlimi

Bertrand

2022

Preprint

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“…Next, the medium was replaced with 100 µL fresh DMEM with 2% (v/v) FBS or fresh DMEM with 2% (v/v) FBS containing: (1) 6 µM sparstolonin B or (2) 200 µM TL2-C29 (InvivoGen, San Diego, CA, USA). After 30 min, the medium was replaced again with fresh DMEM supplemented with 2% (v/v) FBS or DMEM supplemented with 2% (v/v) FBS and containing (1) 2 µg/mL LTA, (2) 1 µM BacSp222, (3) 1 µM suc-K20-BacSp222, (4) 1 µM -fM-BacSp222, (5) 6 µM sparstolonin B, (6) 6 µM sparstolonin B and 2 µg/mL LTA, (7) 6 µM sparstolonin B and 1 µM BacSp222, (8) 6 µM sparstolonin B and 1 µM suc-K20-BacSp222, (9) 6 µM sparstolonin B and 1 µM -fM-BacSp222, (10) 200 µM TL2-C29, (11) 200 µM TL2-C29 and 2 µg/mL LTA, (12) 200 µM TL2-C29 and 1 µM BacSp222, (13) 200 µM TL2-C29 and 1 µM suc-K20-BacSp222, ( 14) 200 µM TL2-C29 and 1 µM -fM-BacSp222. After 6 h, the media were collected for TNF concentration analysis using the ELISA test described above.…”

Section: Inhibition Of Murine Tlr2 By the Selected Antagonistsmentioning

confidence: 99%

“…They are peptides and proteins that kill or inhibit the growth of similar or closely related bacterial strains [9]. All bacteriocins are synthesized on ribosomes, and this fact fundamentally distinguish them from peptide antibiotics-which are synthesized on specialized enzyme complexes, called non-ribosomal peptide synthetases (NRPS) [10]. It is estimated that almost every bacterial specie can produce at least one kind of bacteriocins, and, assuming such widespread prevalence, these molecules appear to be critical factors influencing the proper microbiome composition of the skin, mucous membranes, gastrointestinal and urogenital tracts [11].…”

Section: Introductionmentioning

confidence: 99%

BacSp222 bacteriocin as a novel ligand for TLR2/TLR6 heterodimer

et al. 2023

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Objective and design BacSp222 bacteriocin is a bactericidal and proinflammatory peptide stimulating immune cells to produce selected cytokines and NO in NF-ĸB dependent manner. This study aims to identify the receptor which mediates this activity. Methods We applied fluorescently labeled BacSp222 and a confocal microscopy imaging to analyze the direct interaction of the bacteriocin with the cells. Reporter HEK-Blue cells overexpressing human toll-like receptors (TLR2, TLR4, TLR5 or TLR2/TLR1 and TLR2/TLR6 heterodimers) were stimulated with BacSp222, and then the activity of NF-ĸB-dependent secreted embryonic alkaline phosphatase (SEAP) was measured. In turn, formylated peptide receptor (FPR) or TLR2 antagonists were used to verify bacteriocin-stimulated TNF production by murine monocyte-macrophage cell lines. Results BacSp222 undergoes internalization into cells without disturbing the cell membrane. FPR antagonists do not affect TNF produced by BacSp222-stimulated murine macrophage-like cells. In contrast, BacSp222 stimulates NF-ĸB activation in HEK-Blue overexpressing TLR2 or TLR2/TLR6 heterodimer, but not TLR2/TLR1, TLR4 or TLR5 receptors. Moreover, TLR2-specific antagonists inhibit NF-ĸB signaling in BacSp222-stimulated HEK-Blue TLR2/TLR6 cells and reduce TNF release by BacSp222-treated RAW 264.7 and P388.D1. Conclusions BacSp222 is a novel ligand for TLR2/TLR6 heterodimer. By binding TLR complex the bacteriocin undergoes internalization, inducing proinflammatory signaling that employs MyD88 and NF-ĸB pathways.

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“…By the middle of the first decade of the 21st Century, it was becoming clear that microbial genome mining could become a major driver to revitalize a moribund natural products discovery and development industry (Baltz, 2008 ). In the ensuing years, major advances in genome sequencing technology, bioinformatics, metabolomics, and synthetic biology have accelerated the discovery of new and novel secondary metabolite BGCs for drug development, and are providing an unprecedented source of genetic parts and devices for synthetic biology approaches to combinatorial biosynthesis of complex molecules assembled by NRPS, PKS-I, or mixed NRPS/PKS-I pathways (Baltz, 2018 ; Yuzawa et al, 2018 ; Iacovelli et al, 2021 ; Whitford et al, 2021 ). As with any new technology, advancements are often driven by hypotheses and conjectures that need to be validated or rejected as misconceptions (Baltz, 2019 ).…”

Section: Perspectivementioning

confidence: 99%

Genome mining for drug discovery: progress at the front end

Baltz¹

2021

Journal of Industrial Microbiology and Biotechnology

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Microbial genome mining for drug discovery and development has been accelerating in recent years, driven by technical advancements in genome sequencing, bioinformatics, metabolomics/metabologenomics, and synthetic biology. Microbial genome mining is a multi-step process that starts with the sequencing of microbes that encode multiple secondary metabolites, and identifying new and novel secondary metabolite biosynthetic gene clusters (BGCs) to pursue. The first steps in the process are critical for the overall success, and they encompass the most innovative new technologies to revitalize natural product discovery. As microbial genome mining has matured in recent years, unvalidated conjectures about what microbes to pursue, how to identify legitimate secondary metabolite BGCs, and how to sequence DNA to satisfactory levels of completion have been identified. The solutions to correct the misconceptions around these topics are beginning to be implemented.

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Correction to: Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens

Cited by 5 publications

References 0 publications

Reconciliation and evolution ofPenicillium rubensGenome-Scale Metabolic Networks – What about specialised metabolism?

Reconciliation and evolution ofPenicillium rubensGenome-Scale Metabolic Networks – What about specialised metabolism?

BacSp222 bacteriocin as a novel ligand for TLR2/TLR6 heterodimer

Genome mining for drug discovery: progress at the front end

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