小柯机器人

英国华威大学Christophe Corre和Gregory L. Challis课题组合作的最新研究揭示了细菌激素控制抗生素生产的分子机制。相关论文在线发表在2021年2月3日出版的《自然》杂志上。

研究人员解析了MmfR–2-烷基-4-羟甲基呋喃-3-羧酸（AHFCA）复合物的X衍射晶体结构，揭示了激素识别的结构基础。研究人员还解析了MmfR-操纵子复合物的单粒子冷冻电镜结构，阐明了激素结合后DNA释放的机制。用MmfR突变体和合成的AHFCA类似物进行的DNA结合和释放测定实验确定了各个氨基酸残基和激素官能团在配体识别和DNA释放中的作用。这些发现将有助于合成生物学和新抗生素发现过程中利用放线菌激素及其相关的TetR家族转录阻遏物（TFTR）。

据介绍，放线菌产生大量的抗生素和其他特异的代谢产物，在医学和农业生成过程中具有重要的用途。弥散性激素经常通过结合TFTR来控制此类代谢产物的产生，但其分子基础仍然不清楚。通过AHFCA激素与TFTR MmfR3的结合来诱导链霉菌A3（2）产生甲基霉素。

附：英文原文

Title: Molecular basis for control of antibiotic production by a bacterial hormone

Author: Shanshan Zhou, Hussain Bhukya, Nicolas Malet, Peter J. Harrison, Dean Rea, Matthew J. Belousoff, Hariprasad Venugopal, Paulina K. Sydor, Kathryn M. Styles, Lijiang Song, Max J. Cryle, Lona M. Alkhalaf, Vilmos Flp, Gregory L. Challis, Christophe Corre

Issue&Volume: 2021-02-03

Abstract: Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR–AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR–operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.

DOI: 10.1038/s41586-021-03195-x

Source: https://www.nature.com/articles/s41586-021-03195-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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