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Chemical mutagenesis and high throughput media optimization in Tolypocladium inflatum MTCC-3538 leads to enhanced production of cyclosporine A

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Abstract

Diethyl sulphate-based mutagenesis was performed on fungal strain Tolypocladium inflatum MTCC-3538. Two mutant morphotypes MT1-3538 and MT2-3538 were selected for further chemo-profiling studies. LCMS/MS profiling of fungal crude extract confirmed that the wild-type and mutant strains (MT1-3538, MT2-3538) were competent to produce cyclosporine A. MT2-3538 produced 2.1 fold higher cyclosporine A in comparison to the wild type. Further, LCMS-based high throughput media optimization was performed for MT2-3538 in 20 different media combinations to increase cyclosporine A yield. On the basis of ion-intensity profiling, media combination consisting of Glucose 0.1 g/L; Peptone 0.005 g/L and Valine 0.005 g/L was selected and used for up-scaling purpose. Mutant MT2-3538 with optimized media combination increased cyclosporine yield 16 fold and could potentially be exploited for commercial outcomes.

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Acknowledgements

Sundeep Jaglan gratefully acknowledges the Department of Science Technology (DST), Govt. of India for the financial assistance with Grant No. ECR/2017/001381

Funding

This article is funded by SERB DST INDIA, ECR/2017/001381, Sundeep Jaglan.

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VA executed the experimental work and prepared the original draft of the manuscript. MK did the analytical studies. SM did the formal analysis, supervision, review and editing of the manuscript. SJ contributed for the conceptualization, validation, formal analysis, supervision, editing of the manuscript and funding acquisition. All the authors read and approved the final manuscript.

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Correspondence to Sundeep Jaglan.

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The authors declare that they have no conflict of interest in the publication.

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Abrol, V., Kushwaha, M., Mallubhotla, S. et al. Chemical mutagenesis and high throughput media optimization in Tolypocladium inflatum MTCC-3538 leads to enhanced production of cyclosporine A. 3 Biotech 12, 158 (2022). https://doi.org/10.1007/s13205-022-03219-x

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  • DOI: https://doi.org/10.1007/s13205-022-03219-x

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