Identification and Predictions Regarding the Biosynthesis Pathway of Polyene Macrolides Produced by Streptomyces roseoflavus Men-myco-93-63

Identification and Predictions Regarding the Biosynthesis Pathway of Polyene Macrolides Produced by Streptomyces roseoflavus Men-myco-93-63
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DOI:
10.1128/aem.03157-20
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发表时间:
2021-05-01
影响因子:
4.4
通讯作者:
Liu, Daqun
Liu, Daqun
中科院分区:
生物学2区
文献类型:
--
作者:
Han, Xing;Wang, Jiao;Liu, Daqun

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从马铃薯疮痂病自然抑制土壤中分离得到的玫瑰色链霉菌Men-myco-9363的发酵液中分离得到一组多烯大环内酯类化合物,主要由两种成分组成。其中一种大环内酯是1968年首次报道的roflamycoin,另一种是一种名为Men-myco-A的新化合物,它比roflamycoin多一个亚甲基单元。他们一起被指定为RM。这组抗生素对17种植物病原真菌具有广谱的体外抗真菌活性,其50%有效浓度(EC 50)为2.05 ~ 7.09 μ g/ml,90%有效浓度(EC 90)为4.32 ~ 54.45 μ g/ml,表明它们在植物病害防治中具有潜在的应用价值。此外,通过对聚酮酶(PKSs)的模块和结构域分析,结合基因失活实验结果,确定了它们的生物合成基因簇,并提出了相关的生物合成装配线。重要提示玫瑰色链霉菌Men-myco-93-63是本实验室研究多年的生防菌株,对多种作物病害具有良好的抑制作用。因此,鉴定抗菌代谢物是必要的,也是我们的主要目标。在这项工作中,结合化学、生物信息学和分子生物学方法来鉴定活性代谢物的结构和生物合成。本工作为植物病害的生物防治提供了一种新的替代药剂,并有助于通过基因工程提高抗生素的性质和产量。
A group of polyene macrolides mainly composed of two constituents was isolated from the fermentation broth of Streptomyces roseoflavus Men-myco-9363, which was isolated from soil where potato scabs were repressed naturally. One of these macrolides was roflamycoin, which was first reported in 1968, and the other was a novel compound named Men-myco-A, which had one methylene unit more than roflamycoin. Together, they were designated RM. This group of antibiotics exhibited broad-spectrum antifungal activities in vitro against 17 plant-pathogenic fungi, with 50% effective concentrations (EC50) of 2.05 to 7.09 mu g/ml and 90% effective concentrations (EC90) of 4.32 to 54.45 mu g/ml, which indicates their potential use in plant disease control. Furthermore, their biosynthetic gene cluster was identified, and the associated biosynthetic assembly line was proposed based on a module and domain analysis of polyketide synthases (PKSs), supported by findings from gene inactivation experiments.IMPORTANCE Streptomyces roseoflavus Men-myco-93-63 is a biocontrol strain that has been studied in our laboratory for many years and exhibits a good inhibitory effect in many crop diseases. Therefore, the identification of antimicrobial metabolites is necessary and our main objective. In this work, chemical, bioinformatic, and molecular biological methods were combined to identify the structures and biosynthesis of the active metabolites. This work provides a new alternative agent for the biological control of plant diseases and is helpful for improving both the properties and yield of the antibiotics via genetic engineering.