Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast

doi:10.1007/s13659-021-00304-1

Natural Products and Bioprospecting ›› 2021, Vol. 11 ›› Issue (4): 431-445.DOI: 10.1007/s13659-021-00304-1

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Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast

Richard Alexander Lewis¹, Jenileima Devi¹, Katherine Green¹, Juanjuan Li², Adam Hopkins¹, Jacqueline Hayles³, Paul Nurse³, Jeff Errington¹, Nicholas Edward Ellis Allenby¹

1 Demuris Ltd, The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK;
2 University of Southampton, University Road, Southampton SO17 1BJ, UK;
3 Cell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

Received:2021-01-28 Accepted:2021-04-06 Online:2021-07-30 Published:2021-08-24
Contact: Richard Alexander Lewis
Supported by:
We thank Dr J. Gray of the ICaMB Pinnacle laboratory, Newcastle University for assistance with mass spectrometry. This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001121), the UK Medical Research Council (FC001121), and the Wellcome Trust (FC001121). In addition, this work was supported by a Wellcome Trust grant to P.N. (Grant Number 093917), and Demuris Ltd.

Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast

Richard Alexander Lewis¹, Jenileima Devi¹, Katherine Green¹, Juanjuan Li², Adam Hopkins¹, Jacqueline Hayles³, Paul Nurse³, Jeff Errington¹, Nicholas Edward Ellis Allenby¹

1 Demuris Ltd, The Biosphere, Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, UK;
2 University of Southampton, University Road, Southampton SO17 1BJ, UK;
3 Cell Cycle Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

通讯作者: Richard Alexander Lewis
基金资助:
We thank Dr J. Gray of the ICaMB Pinnacle laboratory, Newcastle University for assistance with mass spectrometry. This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001121), the UK Medical Research Council (FC001121), and the Wellcome Trust (FC001121). In addition, this work was supported by a Wellcome Trust grant to P.N. (Grant Number 093917), and Demuris Ltd.

Abstract

Abstract: This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a “rounded” or “small” cellular morphological phenotype. Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain, SAK950 showed that many induced a “rounded” phenotype. We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes. We show that five of the strains produced streptothricin and that 26 strains produced polyenes, including fungichromin, filipin and candicidin, the last of which was produced by 24 strains. A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S. albidofl avus whilst those that additionally produced streptothricin were related to S. enissocaesilis. A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern. The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S. pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.

Key words: Actinomycetes, Schizosaccharomyces pombe, Morphology, Phenotype, Antifungal, Polyene

摘要： This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a “rounded” or “small” cellular morphological phenotype. Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain, SAK950 showed that many induced a “rounded” phenotype. We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes. We show that five of the strains produced streptothricin and that 26 strains produced polyenes, including fungichromin, filipin and candicidin, the last of which was produced by 24 strains. A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S. albidofl avus whilst those that additionally produced streptothricin were related to S. enissocaesilis. A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern. The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S. pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.

关键词: Actinomycetes, Schizosaccharomyces pombe, Morphology, Phenotype, Antifungal, Polyene

Richard Alexander Lewis, Jenileima Devi, Katherine Green, Juanjuan Li, Adam Hopkins, Jacqueline Hayles, Paul Nurse, Jeff Errington, Nicholas Edward Ellis Allenby. Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast[J]. Natural Products and Bioprospecting, 2021, 11(4): 431-445.

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Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast

Screening and Purification of Natural Products from Actinomycetes that Induce a “Rounded” Morphological Phenotype in Fission Yeast

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