Discovery of “heat shock metabolites” produced by thermotolerant actinomycetes in high-temperature culture

Saito, Shun; Kato, Wataru; Ikeda, Hiroaki; Katsuyama, Yoshihiko; Ohnishi, Yasuo; Imoto, Masaya

doi:10.1038/s41429-020-0279-4

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…For example, recently 18 types of thermotolerant actinomycetes were cultured between 30 and 45°C, and secondary metabolite production was compared. As a result, it was found that 131 secondary metabolites were produced when the actinomycetes were cultured at high temperature (Saito et al, 2020 ). Production of several secondary metabolites was induced in order to deal with the changed physical culture condition, as in the case of Nocardiopsis gilva YIM 90087 that accumulates ectoine and hydroxyectoine under salt stress conditions in order to regulate osmotic pressure (Han et al, 2018 ).…”

Section: Conventional Strategies For Awakening Silent Smbgcsmentioning

confidence: 99%

Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture

Kim

Lee

Hwang

et al. 2021

Journal of Industrial Microbiology and Biotechnology

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Actinomycetes are a rich source of bioactive natural products important for novel drug leads. Recent genome mining approaches have revealed an enormous number of secondary metabolite biosynthetic gene clusters (smBGCs) in actinomycetes. However, under standard laboratory culture conditions, many smBGCs are silent or cryptic. To activate these dormant smBGCs, several approaches, including culture-based or genetic engineering-based strategies, have been developed. Above all, coculture is a promising approach to induce novel secondary metabolite production from actinomycetes by mimicking an ecological habitat where cryptic smBGCs may be activated. In this review, we introduce coculture studies that aim to expand the chemical diversity of actinomycetes, by categorizing the cases by the type of coculture partner. Furthermore, we discuss the current challenges that need to be overcome to support the elicitation of novel bioactive compounds from actinomycetes.

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Section: Conventional Strategies For Awakening Silent Smbgcsmentioning

confidence: 99%

Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture

Kim

Lee

Hwang

et al. 2021

Journal of Industrial Microbiology and Biotechnology

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“…These compounds are ''discoverable'' as they are either constitutively expressed or activated in response to a variation in nutrient availability or cell culture conditions in the lab, such as pH or temperature. 8,9 As only a handful of microbes are readily cultured under standard laboratory conditions, biodiscovery pipelines are limited in their ability to characterise unusual microbial metabolism. Amongst known cultivable microorganisms, Streptomycetes are Gram-positive Actinobacteria that offer a propitious platform for novel antimicrobial discovery.…”

Section: Introductionmentioning

confidence: 99%

Multi-omic characterisation ofStreptomyces hygroscopicusNRRL 30439: detailed assessment of its secondary metabolic potential

et al. 2022

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“…10,11 In our previous research, we found that high-temperature culturing of an actinomycete activated otherwise silent SMBGCs. 12 A total of 57 thermotolerant actinomycetes capable of growing at 45 °C were obtained from an in-house actinomycete library (3160 strains). These strains were cultivated at 30 or 45 °C using various media, and many metabolites produced only in the 45 °C cultures were discovered by LC/MS analysis.…”

Section: ■ Introductionmentioning

confidence: 99%

Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses

et al. 2022

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Dihydromaniwamycin E (1), a new maniwamycin derivative featuring an azoxy moiety, has been isolated from the culture extract of thermotolerant Streptomyces sp. JA74 along with the known analogue maniwamycin E (2). Compound 1 is produced only by cultivation of strain JA74 at 45 °C, and this type of compound has been previously designated a “heat shock metabolite (HSM)” by our research group. Compound 2 is detected as a production-enhanced metabolite at high temperature. Structures of 1 and 2 are elucidated by NMR and MS spectroscopic analyses. The absolute structure of 1 is determined after the total synthesis of four stereoisomers. Though the absolute structure of 2 has been proposed to be the same as the structure of maniwamycin D, the NMR and the optical rotation value of 2 are in agreement with those of maniwamycin E. Therefore, this study proposes a structural revision of maniwamycins D and E. Compounds 1 and 2 show inhibitory activity against the influenza (H1N1) virus infection of MDCK cells, demonstrating IC50 values of 25.7 and 63.2 μM, respectively. Notably, 1 and 2 display antiviral activity against SARS-CoV-2, the causative agent of COVID-19, when used to infect 293TA and VeroE6T cells, with 1 and 2 showing IC50 values (for infection of 293TA cells) of 19.7 and 9.7 μM, respectively. The two compounds do not exhibit cytotoxicity in these cell lines at those IC50 concentrations.

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Discovery of “heat shock metabolites” produced by thermotolerant actinomycetes in high-temperature culture

Cited by 19 publications

References 29 publications

Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture

Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture

Multi-omic characterisation ofStreptomyces hygroscopicusNRRL 30439: detailed assessment of its secondary metabolic potential

Dihydromaniwamycin E, a Heat-Shock Metabolite from Thermotolerant Streptomyces sp. JA74, Exhibiting Antiviral Activity against Influenza and SARS-CoV-2 Viruses

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