Engineering the biosynthesis of fungal nonribosomal peptides

Zhang, Liwen; Wang, Chen; Chen, Kang; Zhong, Weimao; Xu, Yuquan; Molnár, István

doi:10.1039/d2np00036a

Cited by 19 publications

(18 citation statements)

References 137 publications

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“…Notably, many fungal NRPSs utilize a terminal condensation (C T ) domain for macrocyclization and peptide chain release, , whereas thioesterase (TE) domains are generally responsible for such reactions in bacterial NRPSs . The modular nature of NRPSs has inspired researchers to rationally engineer NRPS assembly lines to provide important insights into successful NPRS design, particularly in bacterial systems. , Nevertheless, there is a long way to go before we are able to create designer NRPSs with any desired molecular architecture. To that end, further characterization of NRP biosynthesis, particularly in less studied fungal biosynthetic machinery, will contribute to a deeper understanding and future engineering of NRPSs.…”

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confidence: 99%

Biosynthetic Characterization, Heterologous Production, and Genomics-Guided Discovery of GABA-Containing Fungal Heptapeptides

et al. 2023

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confidence: 99%

Biosynthetic Characterization, Heterologous Production, and Genomics-Guided Discovery of GABA-Containing Fungal Heptapeptides

et al. 2023

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“…The flexibility of the seventh and ninth amino acid residues, as well as the presence of d -amino acid and multiple N -methylated residues in 1 – 4 , strongly suggests a nonribosomal origin of these PNPs . Bioinformatic analysis of the sequenced genome of Sesquicilium sp.…”

Section: Resultsmentioning

confidence: 99%

Mass Spectrometry-Guided Discovery of Multi-N-Methylated Cyclodecapeptides Auyuittuqamides E–H from Sesquicillium sp. QL0466

Xiao

et al. 2023

J. Nat. Prod.

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Mass spectrometry-based dereplication and prioritization led to the discovery of four multi-N-methylated cyclodecapeptides, auyuittuqamides E–H (1–4), from a soil-derived Sesquicillium sp. The planar structures of these compounds were elucidated based on analysis of HRESIMS and NMR data. Absolute configurations of the chiral amino acid residues were assigned by a combination of the advanced Marfey’s method, chiral-phase LC-MS analysis, and J-based configuration analysis, revealing that 1–4 contain both d- and l-isomers of N-methylleucine (MeLeu). Differentiation of d- and l-MeLeu in the sequence was achieved by advanced Marfey’s analysis of the diagnostic peptide fragments generated from partial hydrolysis of 1. Bioinformatic analysis identified a putative biosynthetic gene cluster (auy) for auyuittuqamides E–H, and a plausible biosynthetic pathway was proposed. These newly identified fungal cyclodecapeptides (1–4) displayed in vitro growth inhibitory activity against vancomycin-resistant Enterococcus faecium with MIC values of 8 μg/mL.

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“…The NRPSs enzymatic complex also has three main domains. The adenylation domain (A), which through ATP will adenylate amino acids; the peptidyl carrier protein domain (T), responsible for the binding of a thioester group to the nascent chain; and finally, the condensation domain (C), which catalyzes the peptide bonds in the nascent chain and the amino acids [ 77 , 78 ]. After the beginning of the synthesis, structural changes such as epimerization, n-methylation, cyclization, acylation, glycosylation, hydroxylation, and halogenation occur [ 79 ].…”

Section: Aspects Of Secondary Metabolism Pathways In Microorganismsmentioning

confidence: 99%

Overview of Bioactive Fungal Secondary Metabolites: Cytotoxic and Antimicrobial Compounds

et al. 2022

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Microorganisms are known as important sources of natural compounds that have been studied and applied for different purposes in distinct areas. Specifically, in the pharmaceutical area, fungi have been explored mainly as sources of antibiotics, antiviral, anti-inflammatory, enzyme inhibitors, hypercholesteremic, antineoplastic/antitumor, immunomodulators, and immunosuppressants agents. However, historically, the high demand for new antimicrobial and antitumor agents has not been sufficiently attended by the drug discovery process, highlighting the relevance of intensifying studies to reach sustainable employment of the huge world biodiversity, including the microorganisms. Therefore, this review describes the main approaches and tools applied in the search for bioactive secondary metabolites, as well as presents several examples of compounds produced by different fungi species with proven pharmacological effects and additional examples of fungal cytotoxic and antimicrobial molecules. The review does not cover all fungal secondary metabolites already described; however, it presents some reports that can be useful at any phase of the drug discovery process, mainly for pharmaceutical applications.

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Engineering the biosynthesis of fungal nonribosomal peptides

Abstract: Fungal nonribosomal peptides (NRPs) and the related polyketide–nonribosomal peptide hybrid products (PK–NRPs) are a prolific source of bioactive compounds, some of which have been developed into essential drugs.

Cited by 19 publications

References 137 publications

Biosynthetic Characterization, Heterologous Production, and Genomics-Guided Discovery of GABA-Containing Fungal Heptapeptides

Biosynthetic Characterization, Heterologous Production, and Genomics-Guided Discovery of GABA-Containing Fungal Heptapeptides

Mass Spectrometry-Guided Discovery of Multi-N-Methylated Cyclodecapeptides Auyuittuqamides E–H from Sesquicillium sp. QL0466

Overview of Bioactive Fungal Secondary Metabolites: Cytotoxic and Antimicrobial Compounds

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