{"title":"放线菌LHW52806生物合成潜力的基因组分析","authors":"Hui Hong, Die Zhang, Hou-Wen Lin, Lei Li","doi":"10.1007/s10528-025-11195-z","DOIUrl":null,"url":null,"abstract":"<p><p>Actinoalloteichus caeruleus, the type species of the rare actinomycete genus Actinoalloteichus, was found to produce various classes of bioactive compounds including bipyridine, β-carboline and cyclolipopeptides. Although the chemistry of natural products from A. caeruleus has been well studied over the past two decades, the complete genomes of this talent species along with its secondary metabolic potential was poorly reported. In this work, the complete genome sequence of Actinoalloteichus sp. LHW52806, the only producer of Marinacarboline glucuronic and Cyanogripeptides, was sequenced and the biosynthetic potential was investigated by a genome mining approach. Genomic analyses indicate a circular chromosome consisting of 6,184,314 bp with a G + C content of 72.27%. The dDDH and ANI values based on genome sequences between strain LHW52806 and the type strain, Actinoalloteichus caeruleus NRRL B-2194<sup>T</sup>, were 93.1% and 99.2%, respectively, confirmed the species assignment. Combined analysis using antiSMASH and PRISM identified 27 biosynthetic gene clusters (BGCs) responsible for secondary metabolite. Among these, only 10 BGCs exhibited high similarities to known clusters in the MIBIG database. The remaining clusters are predicted to synthesize novel natural products, encompassing nonribosomal peptides (NRPs), polyketides (PKs), lassopeptides, lantibiotics, and guanidinotides, suggesting substantial biosynthetic potential. The candidate BGC for β-carboline alkaloids was identified in the genome and a biosynthetic pathway of marinacarboline glucuronic was proposed. Guided by the bioinformatic analysis on the BGCs, a series of polycyclic tetramate macrolactams (PTMs) was found by LC-MS in the fermentation extracts of A. caeruleus LHW52806, with 30,31-dihydrofrontalamide A (DHFA) isolated and identified. These findings advance comprehension of secondary metabolite biosynthesis in A. caeruleus, while simultaneously establishing a foundation for novel natural products discovery.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genomic Insights of Biosynthetic Potential from Actinoalloteichus caeruleus LHW52806, a Promising Actinomycete for Natural Product Discovery.\",\"authors\":\"Hui Hong, Die Zhang, Hou-Wen Lin, Lei Li\",\"doi\":\"10.1007/s10528-025-11195-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Actinoalloteichus caeruleus, the type species of the rare actinomycete genus Actinoalloteichus, was found to produce various classes of bioactive compounds including bipyridine, β-carboline and cyclolipopeptides. Although the chemistry of natural products from A. caeruleus has been well studied over the past two decades, the complete genomes of this talent species along with its secondary metabolic potential was poorly reported. In this work, the complete genome sequence of Actinoalloteichus sp. LHW52806, the only producer of Marinacarboline glucuronic and Cyanogripeptides, was sequenced and the biosynthetic potential was investigated by a genome mining approach. Genomic analyses indicate a circular chromosome consisting of 6,184,314 bp with a G + C content of 72.27%. The dDDH and ANI values based on genome sequences between strain LHW52806 and the type strain, Actinoalloteichus caeruleus NRRL B-2194<sup>T</sup>, were 93.1% and 99.2%, respectively, confirmed the species assignment. Combined analysis using antiSMASH and PRISM identified 27 biosynthetic gene clusters (BGCs) responsible for secondary metabolite. Among these, only 10 BGCs exhibited high similarities to known clusters in the MIBIG database. The remaining clusters are predicted to synthesize novel natural products, encompassing nonribosomal peptides (NRPs), polyketides (PKs), lassopeptides, lantibiotics, and guanidinotides, suggesting substantial biosynthetic potential. The candidate BGC for β-carboline alkaloids was identified in the genome and a biosynthetic pathway of marinacarboline glucuronic was proposed. Guided by the bioinformatic analysis on the BGCs, a series of polycyclic tetramate macrolactams (PTMs) was found by LC-MS in the fermentation extracts of A. caeruleus LHW52806, with 30,31-dihydrofrontalamide A (DHFA) isolated and identified. 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引用次数: 0
摘要
放线菌(Actinoalloteichus caeruleus)是稀有放线菌属放线菌的模式种,能产生联吡啶、β-碳碱和环脂肽等多种生物活性化合物。尽管在过去的二十年里,人们对小毛藻天然产物的化学性质进行了很好的研究,但对这一天才物种的完整基因组及其次生代谢潜力的报道却很少。本文对唯一一种产糖醛酸和氰胺肽的植物Actinoalloteichus sp. LHW52806进行了全基因组测序,并利用基因组挖掘方法研究了其生物合成潜力。基因组分析表明,该染色体为环状,全长6184314 bp, G + C含量为72.27%。菌株LHW52806与类型菌株Actinoalloteichus caeruleus NRRL B-2194T基因组序列的dDDH和ANI值分别为93.1%和99.2%,证实了该菌株的种归属。结合antiSMASH和PRISM分析,鉴定出27个与次生代谢物有关的生物合成基因簇(bgc)。其中,只有10个bgc与MIBIG数据库中的已知集群具有高度相似性。预计剩余的簇将合成新的天然产物,包括非核糖体肽(nrp)、多酮(PKs)、多肽、抗生素和胍苷,表明具有巨大的生物合成潜力。在基因组中鉴定了β-碳碱类生物碱的候选BGC,并提出了海洋碳碱类葡萄糖醛酸的生物合成途径。在生物信息学分析的指导下,采用LC-MS技术,从a . caeruleus LHW52806发酵提取物中分离鉴定了一系列多环四乙酸酯内酰胺(PTMs),其中30,31-二氢frontalamide a (DHFA)得到鉴定。这些发现促进了对小毛蚶次生代谢物生物合成的理解,同时为发现新的天然产物奠定了基础。
Genomic Insights of Biosynthetic Potential from Actinoalloteichus caeruleus LHW52806, a Promising Actinomycete for Natural Product Discovery.
Actinoalloteichus caeruleus, the type species of the rare actinomycete genus Actinoalloteichus, was found to produce various classes of bioactive compounds including bipyridine, β-carboline and cyclolipopeptides. Although the chemistry of natural products from A. caeruleus has been well studied over the past two decades, the complete genomes of this talent species along with its secondary metabolic potential was poorly reported. In this work, the complete genome sequence of Actinoalloteichus sp. LHW52806, the only producer of Marinacarboline glucuronic and Cyanogripeptides, was sequenced and the biosynthetic potential was investigated by a genome mining approach. Genomic analyses indicate a circular chromosome consisting of 6,184,314 bp with a G + C content of 72.27%. The dDDH and ANI values based on genome sequences between strain LHW52806 and the type strain, Actinoalloteichus caeruleus NRRL B-2194T, were 93.1% and 99.2%, respectively, confirmed the species assignment. Combined analysis using antiSMASH and PRISM identified 27 biosynthetic gene clusters (BGCs) responsible for secondary metabolite. Among these, only 10 BGCs exhibited high similarities to known clusters in the MIBIG database. The remaining clusters are predicted to synthesize novel natural products, encompassing nonribosomal peptides (NRPs), polyketides (PKs), lassopeptides, lantibiotics, and guanidinotides, suggesting substantial biosynthetic potential. The candidate BGC for β-carboline alkaloids was identified in the genome and a biosynthetic pathway of marinacarboline glucuronic was proposed. Guided by the bioinformatic analysis on the BGCs, a series of polycyclic tetramate macrolactams (PTMs) was found by LC-MS in the fermentation extracts of A. caeruleus LHW52806, with 30,31-dihydrofrontalamide A (DHFA) isolated and identified. These findings advance comprehension of secondary metabolite biosynthesis in A. caeruleus, while simultaneously establishing a foundation for novel natural products discovery.
期刊介绍:
Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses.
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