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Production of bioactive cyclotides: a comprehensive overview
Phytochemistry Reviews ( IF 7.3 ) Pub Date : 2020-05-13 , DOI: 10.1007/s11101-020-09682-9
M. Narayani , R. Babu , Anju Chadha , Smita Srivastava

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 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.



中文翻译:

生物活性环糊精的生产:全面概述

环氧化物是一类新兴的富含二硫键的植物环肽,据信出于防御目的存在于植物中。它们出色的热,化学和酶稳定性使其适合用作治疗剂,农用化学品,分子成像探针和用于药物递送的药物支架。迄今为止,已经鉴定并报告了近350种环孢素,而据估计植物中会发生超过150,000种不同的环素。使用当前的化学鉴定方法,甚至可以从粗提物中鉴定出环氧化物。这篇综述将广泛地描述与筛选植物中是否存在环肽有关的最新策略。尽管鉴定植物中的环孢菌素有助于探索其分布,进化,多样性和生物活性,天然植物提取不是这种植物代谢产物生产的可持续和可靠方法。这可以归因于多种原因,例如由于地理和气候条件导致的供应不一致和不均匀。而且,从非本地,稀有和濒危植物中提取代谢物是不可持续的。因此,正在探索不依赖天然来源的体外生产技术,以促进环糊精的商业应用。由于结构复杂,化学合成和基于重组微生物的生产方法提供了有限量的环化物。在植物细胞培养物中生产生物药物肽是一种安全且可商业应用的替代方案,可以克服其中一些挑战。因此,

更新日期:2020-05-13
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