Improved antibiotic production and silent gene activation in Streptomyces diastatochromogenes by ribosome engineering

Shentu, Xuping; Liu, Nannan; Tang, Gu; Tanaka, Yukinori; Ochi, Kozo; Xu, Jianfeng; Yu, Xiaoping

doi:10.1038/ja.2015.123

Cited by 26 publications

(36 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The genetic characterization of rps12 (NCBI accession number: WP_016698050.1), rpl6 (NCBI accession number: WP_026419518.1) and 16S rDNA (NCBI accession number: CP025990; 1052752-1054270) from XC-11G revealed that no clear mutation site was located, which was consistent with previously reported cases [34][35][36][37]. Additionally, the genetic stability of XC-11G in CRM A biosynthesis was then validated by successive fermentation comparisons among three generations from XC-11G ( Fig.…”

Section: Activation Of Crm a Biosynthesis By Gene Expression-directedsupporting

confidence: 89%

Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

Xie

Chen

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC- cam in its genome. Thus, a genome mining work was preformed to activate the strain’s production of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam , ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

show abstract

Section: Activation Of Crm a Biosynthesis By Gene Expression-directedsupporting

confidence: 89%

Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

Xie

Chen

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Two endophytic Streptomycetes EA65 and EA67 were analyzed by LC-MS and they exhibited spectra for 15 bioactive compounds including antibacterial, antifungal, antiprotozoal and anthelmintic compounds. Strain EA65 showed close similarity at the 97% level to a rhizobacterium S. diastatochromogenes , a promising source of antifungal metabolites and novel natural antibiotics and used as biocontrol agents (Shentu et al, 2016 ). S. diastatochromogenes reportedly produces polyketomycin, momofulvenoneA, azdimycin, toyocamycin, concanamycin, and oligomycins.…”

Section: Discussionmentioning

confidence: 99%

Microbial Flora Associated with the Halophyte–Salsola imbricate and Its Biotechnical Potential

et al. 2018

View full text Add to dashboard Cite

Halophytes are associated with the intertidal forest ecosystem of Saudi Arabia and seemingly have an immense potential for yielding useful and important natural products. In this study we have aimed to isolate and characterize the endophytic and rhizospheric bacterial communities from the halophyte, Salsola imbricata, In addition these bacterial strains were identified and selected strains were further studied for bioactive secondary metabolites. At least 168 rhizspheric and endophytic bacteria were isolated and of these 22 were active antagonists against the oomycetous fungal plant pathogens, Phytophthora capsici and Pythium ultimum. Active cultures were mainly identified with molecular techniques (16S r DNA) and this revealed 95.7–100% sequence similarities with relevant type strains. These microorgansims were grouped into four major classes: Actinobacteria, Firmicutes, β-Proteobacteria, and γ-Proteobacteria. Production of fungal cell wall lytic enzymes was detected mostly in members of Actinobacteria and Firmicutes. PCR screening for type I polyketide synthases (PKS-I), type II polyketide synthases (PKS-II) and nonribosomal peptide synthetases (NRPS) revealed 13 of the 22 strains (59%) were positive for at least one of these important biosynthetic genes that are known to be involved in the synthesis of important antibiotics. Four bacterial strains of Actinobacteria with potential antagonistic activity including two rhizobacteria, EA52 (Nocardiopsis sp.), EA58 (Pseudonocardia sp.) and two endophytic bacteria Streptomyces sp. (EA65) and Streptomyces sp. (EA67) were selected for secondary metabolite analyses using LC-MS. As a result, the presence of different bioactive compounds in the culture extracts was detected some of which are already reported for their diverse biological activities including antibiotics such as Sulfamethoxypyridazine, Sulfamerazine, and Dimetridazole. In conclusion, this study provides an insight into antagonistic bacterial population especially the Actinobacteria from S. imbricata, producing antifungal metabolites of medical significance and characterized taxonomically in future.

show abstract

“…The production of toyocamycin, tetramycin A, tetramycin P, and tetrin B were highest (4.1, 7.8, 5.1, and 12.9-fold, respectively) while using paromomycin to induce the mutation. Similarly, rsmG mutant strain of S. diastatochromogenes substantially increased the production of toyocamycin and also activated silent genes involved in the biosynthesis of secondary metabolites [37].…”

Section: Ribosome/rna Polymerase Engineering Approachmentioning

confidence: 96%

Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

et al. 2020

View full text Add to dashboard Cite

Streptomyces spp. are prolific sources of valuable natural products (NPs) that are of great interest in pharmaceutical industries such as antibiotics, anticancer chemotherapeutics, immunosuppressants, etc. Approximately two-thirds of all known antibiotics are produced by actinomycetes, most predominantly by Streptomyces. Nevertheless, in recent years, the chances of the discovery of novel and bioactive compounds from Streptomyces have significantly declined. The major hindrance for obtaining such bioactive compounds from Streptomyces is that most of the compounds are not produced in significant titers, or the biosynthetic gene clusters (BGCs) are cryptic. The rapid development of genome sequencing has provided access to a tremendous number of NP-BGCs embedded in the microbial genomes. In addition, the studies of metabolomics provide a portfolio of entire metabolites produced from the strain of interest. Therefore, through the integrated approaches of different-omics techniques, the connection between gene expression and metabolism can be established. Hence, in this review we summarized recent advancements in strategies for activating cryptic BGCs in Streptomyces by utilizing diverse state-of-the-art techniques.

show abstract

Improved antibiotic production and silent gene activation in Streptomyces diastatochromogenes by ribosome engineering

Cited by 26 publications

References 18 publications

Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

Microbial Flora Associated with the Halophyte–Salsola imbricate and Its Biotechnical Potential

Recent Advances in Strategies for Activation and Discovery/Characterization of Cryptic Biosynthetic Gene Clusters in Streptomyces

Contact Info

Product

Resources

About