Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete.
Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete.
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DOI：
10.1021/acs.jnatprod.8b00394
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发表时间：
2018-09-28
影响因子：
5.1
通讯作者：
Eustáquio AS
中科院分区：
文献类型：
--
作者：
Braesel J;Crnkovic CM;Kunstman KJ;Green SJ;Maienschein-Cline M;Orjala J;Murphy BT;Eustáquio AS
从淡水环境中分离的放线菌是一种未开发的天然产物来源。在这里，我们报告的完整基因组的大湖区衍生小单孢菌菌株B 006，揭示其天然产物生物合成的潜力。使用Illumina和Oxford Nanopore技术对菌株B 006的7兆碱基对染色体进行测序，然后进行桑格测序以闭合剩余的缺口。所有鉴定的生物合成基因簇（BGC）都是手动策划的。鉴定出五种已知的BGC，编码去铁胺、烷基-O −二氢香叶基-甲氧基氢醌、孢子色素、硅黄素和二氮卓霉素，目前正在进行II期临床试验，用于治疗麦-麦二氏综合征和共病癫痫。我们在这里报告说，菌株B 006确实是一个生产商的二氮卓类霉素，并在产量高于以前报道。此外，16个鉴定的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包括一个烯二炔聚酮合酶和一个非典型的大的，36-模块聚酮脱氢酶核糖体肽合成酶BGC。我们开发了小单孢菌B 006的遗传学系统，这将有助于未来BGC的去孤儿化。这项研究是为数不多的尝试报告的淡水来源的放线菌的生物合成能力，并强调这种资源作为一个潜在的水库，为新的天然产品。
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−dihydrogeranyl-methoxyhydroquinone, 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, eleven of the sixteen 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 synthasenonribosomal peptide synthetase BGC. We developed a genetics system for Micromonospora sp. B006 that shall 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.
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影响因子：
3.2
作者：
Awakawa, Takayoshi;Fujita, Nobuyuki;Horinouchi, Sueharu
通讯作者：
Horinouchi, Sueharu
影响因子：
4.6
作者：
Giordano F;Aigrain L;Quail MA;Coupland P;Bonfield JK;Davies RM;Tischler G;Jackson DK;Keane TM;Li J;Yue JX;Liti G;Durbin R;Ning Z
通讯作者：
Ning Z
影响因子：
4.6
作者：
Carro L;Nouioui I;Sangal V;Meier-Kolthoff JP;Trujillo ME;Montero-Calasanz MDC;Sahin N;Smith DL;Kim KE;Peluso P;Deshpande S;Woyke T;Shapiro N;Kyrpides NC;Klenk HP;Göker M;Goodfellow M
通讯作者：
Goodfellow M
DOI：
10.1073/pnas.1714381115
发表时间：
2017-12-26
影响因子：
11.1
作者：
Amos, Gregory C. A.;Awakawa, Takayoshi;Jensen, Paul R.
通讯作者：
Jensen, Paul R.
影响因子：
3.2
作者：
Erb, Annette;Luzhetskyy, Andriy;Bechthold, Andreas
通讯作者：
Bechthold, Andreas