通过缺失spinosyn基因簇激活棘糖多孢子虫的隐生生物合成途径:诱导隐生和生物活性天然产物。

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Adzemye Fovennso Bridget, Rabin Budhathoki, Chen Huo, Soniya Joshi, Niranjan Parajuli, Jae Kyung Sohng, Ki Hyun Kim
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引用次数: 0

摘要

棘糖多孢子菌(Saccharopolyspora spinosa)是假心科的一员,最初是从维尔京群岛的土壤中分离出来的,以生产棘糖甙(一种广谱杀虫次生代谢物)而闻名。虽然对棘豆的研究历来集中在棘豆苷的产生上,但对其基因组编码的次级代谢物的更广泛谱知之甚少。像链霉菌一样,棘孢链球菌也有许多生物合成基因簇(bgc),其中许多在标准实验室条件下仍然是隐藏的。在本研究中,使用热敏载体pKC1139删除spinosyn基因簇,产生突变菌株S. spinosaΔSPN。采用高效液相色谱-高分辨率串联质谱(HRMS/MS)技术对野生型棘叶沙棘菌(B1)和spinosaΔSPN (B2)发酵产物进行了分析。使用基于gnps的分子网络和MestReNova进行数据分析。野生型菌株(B1)共有7种代谢物被推测注释,以spinosyns为主要化合物。相比之下,突变菌株(B2)产生线性和环状脂肽,包括ageostatins和gageopeptin作为主要代谢产物。此外,S. spinosaΔSPN (B2)的粗提取物显示出抗菌活性,可能是由于产生的脂肽,这是众所周知的抗菌特性。这些发现表明,spinosyn基因簇的缺失可以激活隐藏的生物合成途径,从而发现具有潜在医学应用价值的新型生物活性化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Activation of cryptic biosynthetic pathways in Saccharopolyspora spinosa through deletion of the spinosyn gene cluster: induction of cryptic and bioactive natural products.

Saccharopolyspora spinosa, a member of the Pseudonocardiaceae family, was originally isolated from soil in the Virgin Islands and is renowned for producing spinosad, a broad-spectrum insecticidal secondary metabolite. While research on S. spinosa has historically focused on spinosad production, little is known about the broader spectrum of secondary metabolites encoded by its genome. Like Streptomyces, S. spinosa harbors numerous biosynthetic gene clusters (BGCs), many of which remain cryptic under standard laboratory conditions. In this study, the spinosyn gene cluster was deleted using the heat-sensitive vector pKC1139, generating the mutant strain S. spinosaΔSPN. The fermentation products of both the wild-type S. spinosa (B1) and S. spinosaΔSPN (B2) were analyzed through HPLC coupled with high-resolution tandem mass spectrometry (HRMS/MS). Data analysis was conducted using GNPS-based molecular networking and MestReNova. A total of seven metabolites were putatively annotated in the wild-type strain (B1), with spinosyns being the predominant compounds. In contrast, the mutant strain (B2) produced putatively linear and cyclic lipopeptides, including gageostatins and gageopeptins as the major metabolites. Additionally, the crude extract from S. spinosaΔSPN (B2) exhibited antibacterial activity, likely due to the production of lipopeptides, which are known for their antimicrobial properties. These findings indicate that deletion of the spinosyn gene cluster can activate cryptic biosynthetic pathways, leading to the discovery of novel bioactive compounds with potential applications in medicine.

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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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