Identification of tirandamycins as specific inhibitors of the futalosine pathway

Ogasawara, Yasushi; Kondo, Kensuke; Ikeda, Ayumi; Harada, Rikako; Dairi, Tohru

doi:10.1038/ja.2017.22

Cited by 19 publications

(15 citation statements)

References 17 publications

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“…17944 efficiently killed the adult Brugia malayi parasites as a B. malayi asparagine tRNA synthetase inhibitor (Yu et al, 2011; Rateb et al, 2014). A recent study revealed that tirandamycins A and B were identified as specific inhibitors of the futalosine pathway (Ogasawara et al, 2017). The present study uncovered that tirandamycins A and B remarkably inhibited the growth of S. agalactiae HNe0, suggesting the potential of tirandamycins as the anti- S. agalactiae drug candidates.…”

Section: Resultsmentioning

confidence: 99%

Streptomyces tirandamycinicus sp. nov., a Novel Marine Sponge-Derived Actinobacterium With Antibacterial Potential Against Streptococcus agalactiae

et al. 2019

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A novel actinobacterium, strain HNM0039T, was isolated from a marine sponge sample collected at the coast of Wenchang, Hainan, China and its polyphasic taxonomy was studied. The isolate had morphological and chemical characteristics consistent with the genus Streptomyces. Based on the 16S rRNA gene sequence analysis, strain HNM0039T was closely related to Streptomyces wuyuanensis CGMCC 4.7042T (99.38%) and Streptomyces spongiicola HNM0071T (99.05%). The organism formed a well-delineated subclade with S. wuyuanensis CGMCC 4.7042T and S. spongiicola HNM0071T in the Streptomyces 16S rRNA gene tree. Multi-locus sequence analysis (MLSA) based on five house-keeping gene alleles (atpD, gyrB, rpoB, recA, trpB) further confirmed their relationship. DNA–DNA relatedness between strain HNM0039T and its closest type strains, namely S. wuyuanensis CGMCC 4.7042T and S. spongiicola HNM0071T, were 46.5 and 45.1%, respectively. The average nucleotide identity (ANI) between strain HNM0039T and its two neighbor strains were 89.65 and 91.44%, respectively. The complete genome size of strain HNM0039T was 7.2 Mbp, comprising 6226 predicted genes with DNA G+C content of 72.46 mol%. Thirty-one putative secondary metabolite biosynthetic gene clusters were also predicted in the genome of strain HNM0039T. Among them, the tirandamycin biosynthetic gene cluster has been characterized completely. The crude extract of strain HNM0039T exhibited potent antibacterial activity against Streptococcus agalactiae in Nile tilapia. And tirandamycins A and B were further identified as the active components with MIC values of 2.52 and 2.55 μg/ml, respectively. Based on genotypic and phenotypic characteristics, it is concluded that strain HNM0039T represents a novel species of the genus Streptomyces whose name was proposed as Streptomyces tirandamycinicus sp. nov. The type strain is HNM0039T (= CCTCC AA 2018045T = KCTC 49236T).

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Section: Resultsmentioning

confidence: 99%

Streptomyces tirandamycinicus sp. nov., a Novel Marine Sponge-Derived Actinobacterium With Antibacterial Potential Against Streptococcus agalactiae

et al. 2019

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“…3) The biosynthetic pathways for the signalling molecules gamma-butyrolactones (SCB1, 2 and 3) were added [ 31 , 32 ]; secondary metabolite production in Streptomyces (e.g., yCPK) can be activated through these small diffusible molecules, and they are an interesting target for synthetic biology engineering [ 33 , 34 ]. 4) The futalosine pathway, an alternative menaquinone biosynthesis pathway, which was highlighted as incomplete in the previous model [ 22 ], has now been updated following recently published studies [ 35 , 36 ]. 5) The oxidative phosphorylation associated reactions have been manually curated.…”

Section: Resultsmentioning

confidence: 99%

Development and validation of an updated computational model of Streptomyces coelicolor primary and secondary metabolism

2018

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BackgroundStreptomyces species produce a vast diversity of secondary metabolites of clinical and biotechnological importance, in particular antibiotics. Recent developments in metabolic engineering, synthetic and systems biology have opened new opportunities to exploit Streptomyces secondary metabolism, but achieving industry-level production without time-consuming optimization has remained challenging. Genome-scale metabolic modelling has been shown to be a powerful tool to guide metabolic engineering strategies for accelerated strain optimization, and several generations of models of Streptomyces metabolism have been developed for this purpose.ResultsHere, we present the most recent update of a genome-scale stoichiometric constraint-based model of the metabolism of Streptomyces coelicolor, the major model organism for the production of antibiotics in the genus. We show that the updated model enables better metabolic flux and biomass predictions and facilitates the integrative analysis of multi-omics data such as transcriptomics, proteomics and metabolomics.ConclusionsThe updated model presented here provides an enhanced basis for the next generation of metabolic engineering attempts in Streptomyces.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4905-5) contains supplementary material, which is available to authorized users.

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“…The compounds contain a bicyclic ketal and dienoyl tetramic acid moiety. The compounds were found to be able to inhibit RNA polymerase of bacteria and also found to be a specific inhibitor of the futalosine pathway, which is responsible for the synthesis of menaquinone, a crucial component in the electron-transfer system of prokaryotes [ 153 , 154 ].…”

Section: Applications In Aquaculturementioning

confidence: 99%

Bioactive Compounds from Marine Sponges: Fundamentals and Applications

et al. 2021

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Marine sponges are sessile invertebrates that can be found in temperate, polar and tropical regions. They are known to be major contributors of bioactive compounds, which are discovered in and extracted from the marine environment. The compounds extracted from these sponges are known to exhibit various bioactivities, such as antimicrobial, antitumor and general cytotoxicity. For example, various compounds isolated from Theonella swinhoei have showcased various bioactivities, such as those that are antibacterial, antiviral and antifungal. In this review, we discuss bioactive compounds that have been identified from marine sponges that showcase the ability to act as antibacterial, antiviral, anti-malarial and antifungal agents against human pathogens and fish pathogens in the aquaculture industry. Moreover, the application of such compounds as antimicrobial agents in other veterinary commodities, such as poultry, cattle farming and domesticated cats, is discussed, along with a brief discussion regarding the mode of action of these compounds on the targeted sites in various pathogens. The bioactivity of the compounds discussed in this review is focused mainly on compounds that have been identified between 2000 and 2020 and includes the novel compounds discovered from 2018 to 2021.

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Identification of tirandamycins as specific inhibitors of the futalosine pathway

Cited by 19 publications

References 17 publications

Streptomyces tirandamycinicus sp. nov., a Novel Marine Sponge-Derived Actinobacterium With Antibacterial Potential Against Streptococcus agalactiae

Streptomyces tirandamycinicus sp. nov., a Novel Marine Sponge-Derived Actinobacterium With Antibacterial Potential Against Streptococcus agalactiae

Development and validation of an updated computational model of Streptomyces coelicolor primary and secondary metabolism

Bioactive Compounds from Marine Sponges: Fundamentals and Applications

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