Activation and discovery of tsukubarubicin from Streptomyces tsukubaensis through overexpressing SARPs

Wu, Qiliang; Chen, Xin-Ai; Lv, Zhongyuan; Zhang, Xiaoxin; Liu, Yu; Li, Yongquan

doi:10.1007/s00253-021-11344-5

Cited by 9 publications

(5 citation statements)

References 56 publications

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“…Additionally, a cryptic ahbamycin gene cluster of Streptomyces argillaceus was activated by constitutive overexpression of its cluster-situated SARP-encoding gene ( Ye et al, 2023 ). In addition, the overexpression of tsuR1 , a putative uncharacterized SARP-encoding gene, led to the discovery of the antitumour antibiotic tsukubarubicin in S. tsukubaensis ( Wu et al, 2021 ). Similar strategies have been used to activate the production of a novel amide-containing polyene in Streptomyces sp.…”

Section: Biotechnological Application Of Sarpsmentioning

confidence: 99%

The roles of SARP family regulators involved in secondary metabolism in Streptomyces

Yan,

Xia

2024

Front. Microbiol.

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Streptomyces species are best known for their ability to produce abundant secondary metabolites with versatile bioactivities and industrial importance. These metabolites are usually biosynthesized through metabolic pathways encoded by cluster-situated genes. These genes are also known as biosynthetic gene clusters (BGCs) of secondary metabolites. The expression of BGCs is intricately controlled by pyramidal transcriptional regulatory cascades, which include various regulators. Streptomyces antibiotic regulatory proteins (SARPs), a genus-specific family of regulators, are widely distributed and play important roles in regulating the biosynthesis of secondary metabolites in Streptomyces. Over the past decade, the biological functions of SARPs have been extensively investigated. Here, we summarized the recent advances in characterizing the roles of SARPs involved in Streptomyces secondary metabolism from the following three aspects. First, the classification and domain organization of SARPs were summarized according to their size variation. Second, we presented a detailed description of the regulatory mechanisms and modes of action of SARPs involved in secondary metabolism. Finally, the biotechnological application of SARPs was illustrated by improving the production of target secondary metabolites and discovering novel bioactive natural products. This review will help researchers to comprehensively understand the roles of SARPs in secondary metabolite biosynthesis in Streptomyces, which will contribute to building a solid foundation for their future application in synthetic biology.

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Section: Biotechnological Application Of Sarpsmentioning

confidence: 99%

The roles of SARP family regulators involved in secondary metabolism in Streptomyces

Yan,

Xia

2024

Front. Microbiol.

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“…10). 182 Decilorene B (46) harbors the epoxyoxocin ring system in a different regiochemistry appended at C4. 183 Other acetate primed anthracyclines include micromonomycin (47), which contains a 2,3,6-trideoxy sugar with an unusual acyl substitution at C4 0 , 184 and 1-hydroxyauramycin Y (48) (Fig.…”

Section: Reviewmentioning

confidence: 99%

“…107 and 209) and 2 (ref. 111 and 210) is reflected in the fact that two BGCs for each have been identified from different Streptomyces strains, whereas single BGCs have been confirmed for rhodomycin ( 1 ), 155 nogalamycin ( 4 ), 110 cosmomycin ( 26 ), 147 cytorhodin ( 27 ), 146 kosinostatin ( 73 ), 133 aranciamycin ( 59 ), 211 arimetamycin ( 68 ), 196 keyicin ( 43 ), 132 tsukubarubicin ( 45 ), 182 komodoquinone ( 25 ), 150 and steffimycin ( 6 ) 124 pathways (Fig. 14).…”

Section: Discoverymentioning

confidence: 99%

Anthracyclines: biosynthesis, engineering and clinical applications

et al. 2022

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“…Until now, several strategies have been successfully applied to the activation of cryptic gene clusters in Streptomyces , such as manipulation of regulator (Wu et al, 2021; J. Xu, Zhang, et al, 2017), heterologous expression of gene cluster (Kang and Kim, 2021), co‐cultivation (Kim et al, 2021). Ribosome engineering technology was also regarded as an effective strategy for activation of silent gene cluster (Ochi, 2017; Thong et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Double‐reporter‐guided targeted activation of the oxytetracycline silent gene cluster in Streptomyces rimosus M527

Shi

Zhang

et al. 2023

Biotech & Bioengineering

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In Streptomyces rimosus M527, the oxytetracycline (OTC) biosynthetic gene cluster is not expressed under laboratory conditions. In this study a reported‐guided mutant selection (RGMS) procedure was used to activate the cluster. The double‐reporter plasmid pAGT was constructed in which gusA encoding a β‐glucuronidase and tsr encoding a thiostrepton resistance methyltransferase were placed under the control of the native promoter of oxyA gene (PoxyA). Plasmid pAGT was introduced and integrated into the chromosome of S. rimosus M527 by conjugation, yielding initial strain M527‐pAGT. Subsequently, mutants of M527‐pAGT were generated by using ribosome engineering technology. The mutants harboring activated OTC gene cluster were selected based on visual observation of GUS activity and thiostrepton resistance. Finally, mutant M527‐pAGT‐R7 was selected producing OTC in a concentration of 235.2 mg/L. In this mutant transcriptional levels of oxysr genes especial oxyAsr gene were increased compared to wild‐type strain S. rimosus M527. The mutant M527‐pAGT‐R7 showed antagonistic activities against Gram‐negative and Gram‐positive strains. All data indicate that the OTC gene cluster was successfully activated using the RGMS method.

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Activation and discovery of tsukubarubicin from Streptomyces tsukubaensis through overexpressing SARPs

Cited by 9 publications

References 56 publications

The roles of SARP family regulators involved in secondary metabolism in Streptomyces

The roles of SARP family regulators involved in secondary metabolism in Streptomyces

Anthracyclines: biosynthesis, engineering and clinical applications

Double‐reporter‐guided targeted activation of the oxytetracycline silent gene cluster in Streptomyces rimosus M527

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