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Research Contributions from India on Membrane-Modifying Peptides: Motivations from Fungal Peptaibiotics

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Progress in Mycology

Abstract

Peptaibiotics are non-ribosomally synthesized linear peptides that are secondary metabolites of mainly fungal origin. They contain unusual non-protein amino acids, e.g. α-aminoisobutyric acid (Aib) besides possessing modified amino and carboxyl termini. These peptides are capable of altering cell membrane permeability by forming transmembrane voltage-gated ion channels. In India, much of this research was done in Prof. P. Balaram’s group at the Indian Institute of Science, Bengaluru. Initially, peptides based on alamethicin’s sequence were chemically synthesized and their biophysical functions were studied. Further, using fluorescence spectroscopy, aggregation behaviour of synthetic emerimicin and alamethicin fragments in solution was investigated. Subsequently, solution-phase and solid-state conformations of synthetic fragments of suzukacillin, zervamicin and trichogin were probed by circular dichroism, nuclear magnetic resonance spectroscopy and X-ray crystallography. Notably, full-length natural [Leu-1]zervamicin and antiamoebin I were isolated, and their three-dimensional molecular structures were determined by X-ray crystallography. In the latter half of the 1990s, mass spectrometry (MS) was employed to delineate the mechanism of efrapeptin biosynthesis. Tandem MS was applied to obtain insights into the microheterogeneous trichotoxin sequences. A strategy based on tandem MS was devised to distinguish isobaric residues, leucine and isoleucine in zervamicin and antiamoebin. Recently, other groups from India have discovered some new fungal metabolites that belong to this class of peptides.

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Acknowledgements

We thank Prof. P. Balaram, IISc, Bengaluru, for having introduced us to the fascinating field of peptides, particularly peptide secondary metabolites of fungal origin. The authors pursued their PhD research under Prof. P. Balaram’s guidance in Molecular Biophysics Unit, IISc, Bengaluru. We also thank Dr. Devapriya Chowdhury, Jawaharlal Nehru University, New Delhi; Dr. Kiran Lata, IIT, Kanpur; and Deepti Singh, PhD student of GR, for their help in generating some figures for this review/chapter.

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Sabareesh, V., Ramanathan, G. (2021). Research Contributions from India on Membrane-Modifying Peptides: Motivations from Fungal Peptaibiotics. In: Satyanarayana, T., Deshmukh, S.K., Deshpande, M.V. (eds) Progress in Mycology. Springer, Singapore. https://doi.org/10.1007/978-981-16-3307-2_14

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