School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia , Semenyih, Malaysia.
Biotechnol Genet Eng Rev. 2020 Apr;36(1):1-31. doi: 10.1080/02648725.2020.1749818. Epub 2020 Apr 20.
Artemisinin (ART) is an antimalarial compound that possesses a variety of novel biological activities. Due to the low abundance of ART in natural sources, agricultural supply has been erratic, and prices are highly volatile. While heterologous biosynthesis and semi-synthesis are advantageous in certain aspects, these approaches remained disadvantageous in terms of productivity and cost-effectiveness. Therefore, further improvement in ART production calls for approaches that should supplement the agricultural production gap, while reducing production costs and stabilising supply. The present review offers a discussion on the elicitation of plants and/or cultures as an economically feasible yield enhancement strategy to address the global problem of access to affordable ART. Deemed critical for the manipulation of biosynthetic potential, the mechanism of ART biosynthesis is reviewed. It includes a discussion on the current biotechnological solutions to ART production, focusing on semi-synthesis and elicitation. A brief commentary on the possible aspects that influence elicitation efficiency and how oxidative stress modulates ART synthesis is also presented. Based on the critical analysis of current literature, a hypothesis is put forward to explain the possible involvement of enzymes in assisting the final non-enzymatic transformation step leading to ART formation. This review highlights the critical factors limiting the success of elicitor-induced modulation of ART metabolism, that will help inform strategies for future improvement of ART production. Additionally, new avenues for future research based on the proposed hypothesis will lead to exciting perspectives in this research area and continue to enhance our understanding of this intricate metabolic process.
青蒿素（ART）是一种抗疟化合物，具有多种新颖的生物活性。由于天然来源中 ART 的丰度较低，农业供应一直不稳定，价格波动很大。虽然异源生物合成和半合成在某些方面具有优势，但在生产力和成本效益方面仍然存在劣势。因此，进一步提高 ART 的产量需要采取补充农业生产缺口的方法，同时降低生产成本并稳定供应。本综述讨论了植物和/或培养物的诱导作为一种经济可行的提高产量的策略，以解决获得负担得起的 ART 的全球问题。被认为是操纵生物合成潜力的关键，ART 生物合成的机制进行了综述。它包括对 ART 生产的当前生物技术解决方案的讨论，重点是半合成和诱导。还简要讨论了可能影响诱导效率的方面以及氧化应激如何调节 ART 合成。基于对现有文献的批判性分析，提出了一个假设，以解释参与协助导致 ART 形成的最终非酶转化步骤的酶的可能作用。本综述强调了限制诱导剂调节 ART 代谢成功的关键因素，这将有助于为未来提高 ART 生产提供策略。此外，基于提出的假设的未来研究的新途径将为该研究领域带来令人兴奋的前景，并继续加深我们对这一复杂代谢过程的理解。
