Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
Department of Pharmacognosy, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
Molecules. 2021 Dec 27;27(1):142. doi: 10.3390/molecules27010142.
Actinobacterial natural products showed a critical basis for the discovery of new antibiotics as well as other lead secondary metabolites. Varied environmental and physiological signals touch the antibiotic machinery that faced a serious decline in the last decades. The reason was exposed by genomic sequencing data, which revealed that harbor a large portion of silent biosynthetic gene clusters in their genomes that encrypt for secondary metabolites. These gene clusters are linked with a great reservoir of yet unknown molecules, and arranging them is considered a major challenge for biotechnology approaches. In the present paper, we discuss the recent strategies that have been taken to augment the yield of secondary metabolites via awakening these cryptic genes in with emphasis on chemical signaling molecules used to induce the antibiotics biosynthesis. The rationale, types, applications and mechanisms are discussed in detail, to reveal the productive path for the unearthing of new metabolites, covering the literature until the end of 2020.
放线菌天然产物为发现新抗生素和其他先导次级代谢物提供了重要基础。各种环境和生理信号触及抗生素机制，导致过去几十年抗生素严重减少。这一现象的原因通过基因组测序数据得以揭示，这些数据显示，放线菌的基因组中蕴藏着大量沉默的生物合成基因簇，这些基因簇编码次级代谢产物。这些基因簇与大量未知分子密切相关，排列这些基因簇被认为是生物技术方法面临的主要挑战。本文讨论了近年来通过唤醒放线菌中这些隐藏基因来提高次级代谢产物产量的策略，重点讨论了用于诱导抗生素生物合成的化学信号分子。详细讨论了其原理、类型、应用和机制，以揭示挖掘新代谢物的生产途径，涵盖文献截至 2020 年底的内容。
