The Rare Amino Acid Building Block 3-(3-furyl)-Alanine in the Formation of Non-ribosomal Peptides

Maddah, Fayrouz El; Nazir, Mamona; König, Gabriele M.

doi:10.1177/1934578x1701200140

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…The scaffold is further modified by oxygenases, glycosyltransferase and other transferases leading to a high degree of structural diversity ( Hertweck, 2009 ; Brakhage, 2012 ). NRPs, the second largest class, are synthesized by the modular assembly of short carboxylic acids and/or amino acids ( El Maddah et al, 2017 ). They are constituted of both proteinogenic and non-proteinogenic amino acids and show high diversity in terms of length, variation in their functional domains and whether they are cyclized or not ( Keller et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Untargeted Metabolomics Sheds Light on the Secondary Metabolism of Fungi Triggered by Choline-Based Ionic Liquids

et al. 2022

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Fungal secondary metabolites constitute a rich source of yet undiscovered bioactive compounds. Their production is often silent under standard laboratory conditions, but the production of some compounds can be triggered simply by altering the cultivation conditions. The usage of an organic salt – ionic liquid – as growth medium supplement can greatly impact the biosynthesis of secondary metabolites, leading to higher diversity of compounds accumulating extracellularly. This study examines if such supplements, specifically cholinium-based ionic liquids, can support the discovery of bioactive secondary metabolites across three model species: Neurospora crassa, Aspergillus nidulans, and Aspergillus fumigatus. Enriched organic extracts obtained from medium supernatant revealed high diversity in metabolites. The supplementation led apparently to increased levels of either 1-aminocyclopropane-1-carboxylate or α-aminoisobutyric acid. The extracts where bioactive against two major foodborne bacterial strains: Staphylococcus aureus and Escherichia coli. In particular, those retrieved from N. crassa cultures showed greater bactericidal potential compared to control extracts derived from non-supplemented cultures. An untargeted mass spectrometry analysis using the Global Natural Product Social Molecular Networking tool enabled to capture the chemical diversity driven by the ionic liquid stimuli. Diverse macrolides, among other compounds, were putatively associated with A. fumigatus; whereas an unexpected richness of cyclic (depsi)peptides with N. crassa. Further studies are required to understand if the identified peptides are the major players of the bioactivity of N. crassa extracts, and to decode their biosynthesis pathways as well.

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Section: Introductionmentioning

confidence: 99%

Untargeted Metabolomics Sheds Light on the Secondary Metabolism of Fungi Triggered by Choline-Based Ionic Liquids

et al. 2022

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“…Many of these peptides containing nonproteinogenic amino acids have important medical uses. In particular, only a few peptides have been found to bear a nonproteinogenic amino acid, i.e., a 3-(3-furyl)-containing residue, for example, rhizonins and bingchamide B. Rhizonins were reported to be isolated from bacterial endosymbiont Burkholderia endofungorum inside Rhizopus microsporus , a fungus used to prepare fermented food, and bingchamide B was isolated from Streptomyces bingchenggensis . Each of the compounds showed potent cytotoxicity in various cancer cell lines.…”

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confidence: 99%

Mallotumides A–C: Potent Cytotoxic Cycloheptapeptides from the Roots of Mallotus spodocarpus

Sawektreeratana,

Krachangchaeng,

Pittayanurak

et al. 2023

Org. Lett.

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The structures of potent cytotoxic cycloheptapeptides, mallotumides A−C (1−3, respectively) isolated from the roots of Mallotus spodocarpus Airy Shaw, were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by single-crystal X-ray crystallographic data. All three cycloheptapeptides exhibited potent cytotoxicity against various cancer cell lines with IC 50 values ranging from 0.60 to 4.02 nM.

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“…166 Heterocycles can also be embedded into NRPs by the conversion of the proteogenic amino-acids cysteine, serine, and threonine during chain elongation by heterocyclisation (Cy) -domains. These principles can be used to identify the putative BGCs of molecules containing a particular known structural motif arising from the incorporation of rare amino-acids, 167 or reciprocally, can be used to guide the isolation and structural elucidation of a molecule from a newly discovered BGC.…”

Section: Subunit Biosynthesismentioning

confidence: 99%

Metagenomic exploration of Mycale hentscheli microbiome secondary metabolite biosynthesis.

Storey¹

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The natural environment is replete with potent bioactive organic molecules that are produced by the microorganisms that inhabit it. These so-called secondary metabolites provide niche advantages to the producers and have been exploited by mankind for their medicinal and industrial value, especially as antibiotic and antiproliferative agents. One particular environment that has proven to be a rich source of secondary metabolites are certain species of marine sponge, or more specifically, their microbial symbionts. The New Zealand marine sponge Mycale hentscheli is the source of at least three secondary metabolite like molecules, pateamine, peloruside and mycalamide which have spurred much research interest due to their potent bioactivity. However, the exact origin and genetic factors responsible for the production of these molecules remains unknown. In this study undertake a metagenomic drug discovery campaign employing multiple sequencing strategies to reveal that these compounds are produced by multiple members of the sponge’s symbiont microbiome. This is in contrast to previously studied sponges where the secondary metabolites are produced by a single species of microorganism. By analysing the biosynthetic gene clusters in their wider genomic context we found the production of the secondary metabolites was achieved by canonical and non-canonical biosynthetic mechanisms. This approach also shed light on an additional repertoire of biosynthetic potential within this already secondary metabolite-rich sponge and provided the complete genomes of novel taxa. In addition to furthering our understanding of secondary metabolite biosynthesis, we anticipate that the elucidation of the genetic factors responsible for producing the secondary metabolites of M. hentscheli will foster research into their sustainable production by contributing to advances in synthetic biology, heterologous expression and culturing technologies.

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The Rare Amino Acid Building Block 3-(3-furyl)-Alanine in the Formation of Non-ribosomal Peptides

Cited by 5 publications

References 42 publications

Untargeted Metabolomics Sheds Light on the Secondary Metabolism of Fungi Triggered by Choline-Based Ionic Liquids

Untargeted Metabolomics Sheds Light on the Secondary Metabolism of Fungi Triggered by Choline-Based Ionic Liquids

Mallotumides A–C: Potent Cytotoxic Cycloheptapeptides from the Roots of Mallotus spodocarpus

Metagenomic exploration of Mycale hentscheli microbiome secondary metabolite biosynthesis.

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