关键词: Microcystis cyanoHABs metabologenomics natural products secondary metabolism

来  源:   DOI:10.1128/msystems.00334-24

Abstract:
Microcystis spp. are renowned for producing the hepatotoxin microcystin in freshwater cyanobacterial harmful algal blooms around the world, threatening drinking water supplies and public and environmental health. However, Microcystis genomes also harbor numerous biosynthetic gene clusters (BGCs) encoding the biosynthesis of other secondary metabolites, including many with toxic properties. Most of these BGCs are uncharacterized and currently lack links to biosynthesis products. However, recent field studies show that many of these BGCs are abundant and transcriptionally active in natural communities, suggesting potentially important yet unknown roles in bloom ecology and water quality. Here, we analyzed 21 xenic Microcystis cultures isolated from western Lake Erie to investigate the diversity of the biosynthetic potential of this genus. Through metabologenomic and in silico approaches, we show that these Microcystis strains contain variable BGCs, previously observed in natural populations, and encode distinct metabolomes across cultures. Additionally, we find that the majority of metabolites and gene clusters are uncharacterized, highlighting our limited understanding of the chemical repertoire of Microcystis spp. Due to the complex metabolomes observed in culture, which contain a wealth of diverse congeners as well as unknown metabolites, these results underscore the need to deeply explore and identify secondary metabolites produced by Microcystis beyond microcystins to assess their impacts on human and environmental health.IMPORTANCEThe genus Microcystis forms dense cyanobacterial harmful algal blooms (cyanoHABs) and can produce the toxin microcystin, which has been responsible for drinking water crises around the world. While microcystins are of great concern, Microcystis also produces an abundance of other secondary metabolites that may be of interest due to their potential for toxicity, ecological importance, or pharmaceutical applications. In this study, we combine genomic and metabolomic approaches to study the genes responsible for the biosynthesis of secondary metabolites as well as the chemical diversity of produced metabolites in Microcystis strains from the Western Lake Erie Culture Collection. This unique collection comprises Microcystis strains that were directly isolated from western Lake Erie, which experiences substantial cyanoHAB events annually and has had negative impacts on drinking water, tourism, and industry.
摘要:
微囊藻属。以在世界各地的淡水蓝藻有害藻中产生肝毒素微囊藻毒素而闻名,威胁饮用水供应以及公众和环境健康。然而,微囊藻基因组也有许多生物合成基因簇(BGC)编码其他次级代谢产物的生物合成,包括许多具有毒性的。这些BGC中的大多数是未表征的,并且目前缺乏与生物合成产物的联系。然而,最近的实地研究表明,这些BGC中的许多在自然群落中丰富且转录活跃,表明在水华生态和水质中潜在的重要但未知的作用。这里,我们分析了从伊利湖西部分离出的21个xenic微囊藻培养物,以研究该属生物合成潜力的多样性。通过代谢基因组学和计算机模拟方法,我们表明这些微囊藻菌株含有可变的BGC,以前在自然种群中观察到的,并在不同的文化中编码不同的代谢组。此外,我们发现大多数代谢物和基因簇是没有特征的,强调我们对微囊藻的化学库的有限理解。由于在培养物中观察到复杂的代谢组,其中含有大量不同的同源物以及未知的代谢物,这些结果强调需要深入研究和鉴定微囊藻毒素以外的微囊藻毒素产生的次生代谢产物,以评估其对人类和环境健康的影响.重要微囊藻属形成密集的蓝细菌有害藻华(cyanoHAB),并能产生毒素微囊藻毒素,这对世界各地的饮用水危机负有责任。虽然微囊藻毒素非常令人担忧,微囊藻还产生大量的其他次生代谢产物,由于其潜在的毒性,这些代谢产物可能是令人感兴趣的。生态重要性,或药物应用。在这项研究中,我们结合基因组和代谢组学方法来研究负责次生代谢产物生物合成的基因,以及西湖伊利湖文化收藏的微囊藻菌株中产生的代谢产物的化学多样性。这个独特的集合包括直接从伊利湖西部分离的微囊藻菌株,每年都会发生大量的cyanoHAB事件,并对饮用水产生负面影响,旅游,和工业。
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