Production of bioactive cyclotides: a comprehensive overview
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Production of bioactive cyclotides: a comprehensive overview M. Narayani . R. Babu . Anju Chadha . Smita Srivastava
Received: 2 February 2020 / Accepted: 5 May 2020 Ó Springer Nature B.V. 2020
Abstract Cyclotides are an emerging class of disulfide-rich plant cyclic peptides, believed to be present in plants for defence purposes. Their exceptional thermal, chemical and enzymatic stabilities make them suitable as therapeutic agents, agrochemicals, molecular imaging probes and pharmaceutical scaffolds for drug delivery. Nearly 350 cyclotides have been identified and reported to date, while more than 150,000 diverse cyclotides are estimated to occur in plants. With the current chemical identification methodologies, cyclotides can be identified even from crude extracts. This review will extensively describe the latest strategies pertaining to the screening of plants for the presence of cyclotides. Although identification of cyclotides in plants will help to explore their distribution, evolution, diversity and biological activities, natural plant extraction is not a sustainable and reliable method of such plant metabolite production. This can be attributed to several reasons such as inconsistent and non- uniform supply due to geographical and climatic conditions. Moreover, extraction of metabolites from the non-native, rare and endangered plant is not sustainable. Therefore, in vitro production technologies independent of the natural source availability are being explored to
M. Narayani R. Babu A. Chadha S. Srivastava (&) Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India e-mail: [email protected]
facilitate commercial applications of cyclotides. Owing to the complex structure, the chemical synthesis and recombinant microorganism-based methods of production provide limited yields of cyclotides. Production of biopharmaceutical peptides in plant cell cultures is a safe and commercially applicable alternative which can overcome some of these challenges. Hence, strategies for sustainable production of cyclotides by plant in vitro systems is discussed in-depth in this review. Keywords Cyclotides Commercial applications Identification and characterization Production routes Plant cell bioprocess Strategies to enhance production Abbreviations 2,4-D 2,4-Dichlorophenoxyacetic acid AEP Asparaginyl endopeptidase BK Bradykinin Boc tert-butyloxycarbonyl CCK Cyclic cystine knot CTPP C-terminal propeptide CTR C-terminal tail regions CXCR4 G-protein coupled chemokine receptor 4 DAK des-Arg9 -kinestatin DALK des-Arg10-[Leu9]-kallidin EAE Experimental autoimmune encephalomyelitis assay ER Endoplasmic reticulum
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Phytochem Rev
Fmoc GFCKs GPCRs ICKs LDA LNcap LPS MALDIMSI MC4R MCoTI-II MOG NBB NMR NOE NTPP NTR Oak1 PAS PBR1 PC PDI PE PET-CT SPPS TBTO TDZ TLC
9-Fluorenyl methoxy-carbonyl Growth factor cystine knots G protein-coupled receptors Inhibitor cystine knots Larval development a
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