Analysis of the biosynthesis of antibacterial cyclic dipeptides in Nocardiopsis alba

Li, Yongli; Lai, Ying-Mi; Lü, Yi; Yang, Yu‐Liang; Chen, Shawn

doi:10.1007/s00203-014-1015-x

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…For example, HT88 extracts showed antimicrobial activity against test bacteria which is in accordance with our findings; antimicrobial activity of KUMS-C2. Two antibacterial cyclic dipeptides, cyclo(ΔPhe-ΔLeu) (albonoursin) and cyclo(ΔmTyr-ΔLeu), reported from this strain [ 78 ] which is in line with our antibacterial data for the closest isolate. KUMS-C4 was closely related to the Streptomyces durmitorensis strain.…”

Section: Discussionsupporting

confidence: 87%

Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties

et al. 2022

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Background Antibiotic resistance poses a major threat to human health globally. Consequently, new antibiotics are desperately required to discover and develop from unexplored habitats to treat life-threatening infections. Microbial natural products (NP) are still remained as primary sources for the discovery of new antibiotics. Endophytic actinobacteria (EA) which are well-known producers of bioactive compounds could provide novel antibiotic against pathogenic bacteria. This research aimed to isolate EA from the Citrullus colocynthis plant and explore the antibacterial properties of their metabolites against pathogenic bacteria. Results The healthy samples were collected, dissected and surface-sterilized before cultured on four different selection media at 28 °C. Six endophytic actinobacteria were isolated from Citrullus colocynthis plant. They were taxonomically classified into two family namely Streptomycetaceae and Nocardiopsaceae, based on colony morphological features, scanning electron microscope analysis and molecular identification of isolates. This is the first report on the identification of EA form Citrullus colocynthis and their antibacterial activity. The strains generated a chain of vibrio-comma, cubed or cylindrical shaped spores with indenting or smooth surfaces. Three of those were reported as endophytes for the first time. The strain KUMS-C1 showed 98.55% sequence similarity to its closely related strains which constitutes as a novel species/ strain for which the name Nocardiopsis colocynthis sp. was proposed for the isolated strain. Five isolated strains had antagonist activity against S. aureus, P. aeruginosa, and E. coli. Among those, stain KUMS-C6 showed the broadest spectrum of antibacterial activity against all test bacteria, whereas the strain KUMS-C4 had no antibacterial activity. Conclusions NPs have a long history of safe and efficient use for development of pharmaceutical products. Our study highlights that Citrullus colocynthis is an untapped source for the isolation of EA, generating novel and bioactive metabolites by which might lead to discovery of new antibiotic(s). This study reveals the future of new antibiotic developments looks bright against multi-drug resistance diseases by mining under- or unexplored habitats.

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Section: Discussionsupporting

confidence: 87%

Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties

et al. 2022

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“…Another group mainly synthesizes a cFX compound, as AlbC; it contains CDPSs 62, 66, 67, four previously characterized members (Gondry et al, 2009 ; Giessen et al, 2013b ; Li et al, 2014 ; Jacques et al, 2015 ) and a recently identified member that produces mainly cFY (Brockmeyer and Li, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

A Comprehensive Overview of the Cyclodipeptide Synthase Family Enriched with the Characterization of 32 New Enzymes

et al. 2018

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Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100. We detect 16 new cyclodipeptides, one of which containing an arginine which has never been observed previously. This brings to 75 the number of cyclodipeptides formed by CDPSs out of the possible 210 natural ones. We also identify several consensus sequences related to the synthesis of a specific cyclodipeptide, improving the predictive model of CDPS specificity. The improved prediction method enables to propose the main product synthesized for about 80% of the CDPS sequences available in databases and opens the way for the deciphering of CDPS-dependent pathways. Analysis of phylum distribution and predicted activity for all CDPSs identified in databases shows that the experimentally characterized set is representative of the whole family. Our work also demonstrates that some cyclodipeptides, precursors of diketopiperazines with interesting pharmacological properties and previously described as being synthesized by fungal non-ribosomal peptide synthetases, can also be produced by CDPSs in bacteria.

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“…Assembly of the DKP backbone through condensation of two amino acids can be catalyzed by non-ribosomal peptide synthetases (NRPSs) or cyclodipeptide synthases (CDPSs) (Borgman et al 2019;Canu et al 2020). These cyclodipeptides (CDPs) can undergo several tailoring modifications such as methylation, hydroxylation, prenylation, dimerization/coupling, and dehydrogenation, which can enhance their biological and pharmacological activities (Borgman et al 2019;Canu et al 2020;Giessen and Marahiel 2014;Li et al 2014;Yu et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Comparative studies on similarities and differences of cyclodipeptide oxidases for installation of C–C double bonds at the diketopiperazine ring

Mikulski

Schafer

Brockmeyer

et al. 2020

Appl Microbiol Biotechnol

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Cyclodipeptide oxidases (CDOs) perform dehydrogenations on diketopiperazines and play an important role in the cyclodipeptide diversification. In this study, we investigated the two known CDOs AlbA/B and Ndas_1146/7 and one new member, CDO-Np. LC-MS monitoring of 32 cyclodipeptide biotransformations in E. coli revealed good consumption of cyclodipeptides containing aromatic amino acids. Cyclodipeptides consisting solely of aliphatic amino acids were poor substrates. In vitro assays of 34 substrates with crude enzyme extracts and product identification proved that the CDO-Np-containing extract catalyzes the formation of two CC double bonds in many cases. The extracts containing the two other enzymes had lower activities and catalyzed mainly didehydrogenations. For didehydrogenation, the phenylalanyl or tyrosyl site was usually preferred. No or very low acceptance of benzodiazepinediones and a 2,6-diketopiperazine proved the importance of the 2,5diketopiperazine ring. N-Methylation at the diketopiperazine ring or prenylation of the tryptophan-containing cyclodipeptides influences the enzyme activity and product spectrum. Key points • Comparison of catalytic activities of three enzymes; Diverse cyclodipeptides and derivatives as substrates; Determination of double bond formation using 2 H-labeled substrates; Product identification also by interpretation of MS 2 fragmentation pattern.

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Analysis of the biosynthesis of antibacterial cyclic dipeptides in Nocardiopsis alba

Cited by 12 publications

References 33 publications

Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties

Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties

A Comprehensive Overview of the Cyclodipeptide Synthase Family Enriched with the Characterization of 32 New Enzymes

Comparative studies on similarities and differences of cyclodipeptide oxidases for installation of C–C double bonds at the diketopiperazine ring

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