微生物在生长繁殖过程中产生结构多样的次级代谢产物，这些次级代谢产物具有抗菌、抗肿瘤、抗病毒多种生物活性，是现代药物、食品添加剂的重要来源。红树林是一种高盐、高湿度、高辐射、缺氧的独特生态系统，红树林中的微生物具有产生新活性化合物的巨大潜力。目前已从红树林微生物中发现出许多具有生物活性的新型化合物，如生物碱、苯衍生物、环戊酮衍生物、大环内酯类等。本研究从红树林土壤分离筛选出具有抗菌活性的微生物，并对其抗菌次级代谢产物进行研究。

以金黄色葡萄球菌(Staphylococcu saureus ATCC 25923)、枯草芽孢杆菌(Bacillus subtilis 168)、大肠杆菌(Escherichia coli ATCC 25922)和酿酒酵母（Saccharomyces cerevisiae CRY1-2）为指示菌，通过琼脂块法初筛，从红树林土壤样品中筛选出213株活性菌株。经形态学观察后选取出57株菌株为代表性菌株，采用纸片法进行活性复筛，获得13株较高活性菌株。同时，通过16S rRNA基因序列分析对57株菌株进行分类研究。57株菌株分布在厚壁菌门（29株）、变形菌门（7株）和放线菌门（21株）。复筛结果发现具有抗菌活性的菌株均来自放线菌门与厚壁菌门，放线菌门占61.54%，厚壁菌门占38.46%。

选择抗菌活性最好的菌株Micromonospora sp. ZFSF-1M，对其活性产物做进一步研究。采用甲醇萃取结合色谱分离技术对菌株发酵产物中的活性成分分离纯化，获得化合物1和2。通过高分辨电喷雾电离质谱、核磁共振波谱技术对化合物1和2进行结构鉴定，确定二者为新结构的多肽化合物，均由缬氨酸、苏氨酸、异亮氨酸残基组成，通过较特殊连接方式形成具有新型碳骨架结构的“6+7”双环分子。新化合物分别命名为moramincin A和moramincin B，抑菌活性实验发现moramincin B对枯草芽孢杆菌和金黄色葡萄球菌有较强的活性。

为探究moramincin A、B的生物合成过程，对菌株Micromonospora sp. ZFSF-1M进行基因组测序，获得全长为8,080,753 bp的基因组序列。通过antiSMASH（5.2.0）对基因组中的次级代谢产物合成基因簇进行分析，共发现30个次级代谢产物基因簇，并对其中可能与moramincin A、B生物合成相关的基因簇进行了分析。

综上所述，本研究以红树林土壤中的抗菌活性菌株为研究对象，获得了13株较高活性的菌株，为进一步挖掘红树林微生物来源天然产物提供了菌种资源。选择抗菌活性最强的菌株Micromonospora sp. ZFSF-1M进行抗菌活性次级代谢产物研究。对其活性次级代谢产物进行分离鉴定，获得了两个新的多肽化合物moramincin A、B。对菌株Micromonospora sp. ZFSF-1M进行基因组测序，为研究moramincin A、B的生物合成路径提供了基础。

During their growth and reproduction, microorganisms could produce diverse secondary metabolites which have antibacterial, anti-tumor and anti-viral biological activities. These secondary metabolites are an important source of modern medicines and food additives. Mangrove microorganisms, which live inhypoxia environment of high salinity, high humidity and high radiation have great potential to produce new active compounds. Many new compounds with biological activity had been discovered from mangrove microorganisms, such as alkaloids, benzene derivatives, cyclopentanone derivatives, macrolides and so on.

In this thesis, microorganisms with antibacterial activity were isolated and screened from mangrove soil and the secondary metabolites of these strains were further studied. Using Staphylococcu saureus ATCC 25923, Bacillus subtilis 168, Escherichia coli ATCC 25922 and Saccharomyces cerevisiae CRY1-2 as indicator microbes, 213 bioactive strains were isolated from mangrove soil samples by preliminary screening using agar block method. After morphological observation, 57 strains were selected as representative strains and re-screened by filter paper method and 13 strains showed higher activity. Then 16S rRNA gene sequences of the 57 strains were analyzed, and the results indicated that 57 strains were distributed in Firmicutes (29 strains), Proteobacteria (7 strains) and Actinomycetes (21 strains). Using paper diffusion method to re-screened the bioactivities of the 57 strains, 13 strains showed higher activity. The results of the re-screening showed that the strains with antibacterial activity all came from the Actinomycetes and Firmicutes, which accounted for 61.54% and 38.46% of the antibacterial strains respectivly.

Micromonospora sp. ZFSF-1M with the strongest antibacterial activity was selected for further study. The active compounds from the fermentation broth of Micromonospora sp. ZFSF-1M were isolated and purified by methanol extraction and chromatographic separation technologyies, and finally two purified compounds were obtained. The structures of compounds 1 and 2 were elucidated determined by HR-ESI-MS and NMR. The compounds 1 and 2 were both consisted with valine, threonine and isoleucine residues, which formed a new 6+7 bicyclic carbon skeleton. The compounds 1 and 2 were named moramincin A, B respectively. The antibacterial activity assay showed that moramincin B has strong activity against S. aureus ATCC 25923 and B. subtilis 168.

In order to explore the biosynthetic process of moramincins, the genome of the strain Micromonospora sp. ZFSF-1M was sequenced. The total length of the genome was 8080753 bp. The secondary metabolite biosynthetic pathways on the genome were analyzed by online software antiSMASH (5.2.0) and 30 biosynthetic gene clusters were identifed. The gene clusters that might be related to the biosynthesis of moramincins were discussed.

In summry, 13 microbe strains with antibacterial activity were screened and identified from mangrove soil, which provided strain resources for further new natural products mining. The strain Micromonospora sp. ZFSF-1M with the strongest antibacterial activity was selected for further study and two new active compounds moramincin A and moramincin B were purified from the fermentation broth of Micromonospora sp. ZFSF-1M. Furthermore, the genome of Micromonospora sp. ZFSF-1M was sequenced, which laid a foundation for studying the biosynthetic pathway of moramincins.

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