<br>小单孢菌完整基因组。菌株 B006 揭示了密歇根湖放线菌的生物合成潜力。,Journal of Natural Products

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小单孢菌完整基因组。菌株 B006 揭示了密歇根湖放线菌的生物合成潜力。
Journal of Natural Products ( IF 3.3 ) Pub Date : 2018-08-15 , DOI: 10.1021/acs.jnatprod.8b00394
Jana Braesel ₁ , Camila M Crnkovic _{1,

2} , Kevin J Kunstman ₃ , Stefan J Green ₃ , Mark Maienschein-Cline ₄ , Jimmy Orjala ₁ , Brian T Murphy ₁ , Alessandra S Eustáquio ₁

Affiliation

从淡水环境中分离出的放线菌是未经开发的天然产物来源。在这里，我们报告了五大湖衍生的小单孢菌的完整基因组。菌株 B006，揭示了其天然产物生物合成的潜力。使用 Illumina 和 Oxford Nanopore 技术对菌株 B006 的 7 兆碱基对染色体进行测序，然后进行桑格测序以弥补剩余的缺口。所有已识别的生物合成基因簇（BGC）都是手动策划的。鉴定出五种已知的 BGC，编码去铁敏、烷基-O-二氢香叶基甲氧基氢醌、孢子色素、硫黄素和二氮杂霉素，目前正处于治疗 Phelan-McDermid 综合征和共病癫痫的 II 期临床试验中。我们在此报告，菌株 B006 确实是二氮杂霉素的生产者，并且产量高于之前报道的产量。此外，16 个已鉴定的 BGC 中有 11 个是孤儿，其中 8 个在测试的培养条件下具有转录活性。孤儿 BGC 包括烯二炔聚酮合酶和异常大的 36 模块聚酮合酶 - 非核糖体肽合成酶 BGC。我们开发了小单孢菌的遗传学系统。 B006 将有助于未来 BGC 的脱孤。这项研究是报告淡水源放线菌生物合成能力的少数尝试之一，并强调该资源作为新天然产品的潜在库。

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Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete.

Actinomycete bacteria isolated from freshwater environments are an unexplored source of natural products. Here we report the complete genome of the Great Lakes-derived Micromonospora sp. strain B006, revealing its potential for natural product biosynthesis. The 7-megabase pair chromosome of strain B006 was sequenced using Illumina and Oxford Nanopore technologies followed by Sanger sequencing to close remaining gaps. All identified biosynthetic gene clusters (BGCs) were manually curated. Five known BGCs were identified encoding desferrioxamine, alkyl- O-dihydrogeranylmethoxyhydroquinone, a spore pigment, sioxanthin, and diazepinomicin, which is currently in phase II clinical trials to treat Phelan-McDermid syndrome and co-morbid epilepsy. We report here that strain B006 is indeed a producer of diazepinomicin and at yields higher than previously reported. Moreover, 11 of the 16 identified BGCs are orphan, eight of which were transcriptionally active under the culture condition tested. Orphan BGCs include an enediyne polyketide synthase and an uncharacteristically large, 36-module polyketide synthase-nonribosomal peptide synthetase BGC. We developed a genetics system for Micromonospora sp. B006 that will contribute to deorphaning BGCs in the future. This study is one of the few attempts to report the biosynthetic capacity of a freshwater-derived actinomycete and highlights this resource as a potential reservoir for new natural products.

更新日期：2018-08-15

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