链霉菌是放线菌中最大的属,也是链霉菌科的模式属。[1]已发现了500多种链霉菌。[2]和其他放线菌一样,链霉菌属革兰氏阳性,基因组中GC含量高。[3]链霉菌主要是在土壤和腐烂的植被中发现的,大多数链霉菌产生孢子,并因独特的“泥土”味而闻名,这种气味是由一种挥发性代谢物土臭素产生的。
链霉菌的特征是复杂的次级代谢。[3]它们生产超过三分之二在临床上有用的天然抗生素(例如新霉素、环磷酰胺、格里森霉素、瓶菌素和氯霉素)。[4][5]现在不常用的链霉素是直接从链霉菌中得名的。链霉菌是罕见的病原体,但人类感染(如霉菌),可由索马里链球菌和苏丹链球菌引起,而植物感染可由豚鼠链球菌、嗜酸链球菌、膨胀链球菌和疥疮链球菌引起。
链霉菌属包括需氧的革兰氏阳性的丝状细菌,它们产生发育良好带有分枝的营养菌丝(直径在0.5-2.0微米之间)。其形成的复杂基质菌丝体,帮助净化基质中的有机化合物。[10]虽然菌丝和由此产生的气生菌丝是不动的,但流动性是通过孢子的分散来实现的。[10]孢子表面可能是有毛、有皱纹、光滑、多刺或多疣的。[11]在某些物种中,气生菌丝由长而直的丝状体组成,这些细丝或多或少以规则的间隔携带50个或更多孢子,呈螺旋状排列(垂直排列)。顶点的每一个分支在其顶端产生一个伞形花序,它携带两到几个球形到椭圆形、光滑或具皱纹的孢子链。[10]一些菌株在基质菌丝上形成短的孢子链。菌核、皮蛇床子、孢子囊和合成线虫样结构由一些菌株产生。
“天蓝色链霉菌A3(2)”的全基因组测序结果于2002年发表。[12]当时,“天蓝色链球菌”基因组被认为包含了所有细菌中数量最多的基因。[12]染色体长8667507 bp,GC含量为72.1%,预计含有7825个蛋白质编码基因。[12]在分类学上,“天蓝色链霉菌A3(2)”属于紫葡萄孢菌种,不是一个被妥当描述的独立菌种;“天蓝色A3(2)”不应被误认为真正的天蓝色菌(穆勒,种属名称),尽管为了方便起见,它通常被称为天蓝色。[13]
除虫链霉菌的第一个完整基因组序列于2003年完成。[14]这些基因组中的每一个都形成了具有线性结构的染色体,不像大多数细菌基因组那样以圆形染色体的形式存在。[15]疥疮链球菌的基因组序列已经在桑格研究所确定,疥疮链球菌是能够引起马铃薯疮痂病的一个属。它长10.1 Mbp,编码9107个临时基因,是已知最大的链霉菌基因组序列,可能是由于大的致病岛。[15][16]
近年来,生物技术研究人员已经开始使用链霉菌进行蛋白质的异种表达。传统上,大肠杆菌是表达真核基因的首选物种,那是因为它易于理解和操作。[17][18]真核蛋白质在大肠杆菌中的表达可能存在问题。有时,蛋白质折叠不当,这可能导致不溶性、包涵体沉积和产物生物活性的丧失。[19]尽管大肠杆菌菌株具有分泌机制,但这些机制效率低,这会导致分泌物进入周质空间,而革兰氏阳性菌如链霉素类直接分泌到胞外培养基。此外,链霉菌属物种具有比大肠杆菌更有效的分泌机制。分泌系统的性质对于异源表达蛋白质的工业生产是有利的,因为它简化了后续纯化步骤并可提高产量。这些特性和其他特性共同构成链霉素磷酸酯,是大肠杆菌和枯草芽孢杆菌等其他细菌的一种有吸引力的替代品。[19]
到目前为止,已经发现这一属的十个物种对植物具有致病性:[7]
链霉菌属是最大的抗生素生产属,生产抗细菌、抗真菌和抗寄生虫药物,以及多种其他生物活性化合物,如免疫抑制剂。[20]链霉菌产生的几乎所有生物活性化合物都是在与基质菌丝体形成气生菌丝一致的时间内产生的。[10]
链霉菌产生多种具有重要药用价值的抗真菌化合物,包括制霉菌素(来自诺氏链球菌)、两性霉素B(来自诺氏链球菌)和纳他霉素(来自纳他霉素链球菌)。
链霉菌属成员是许多抗菌药物的来源;其中最重要的有:
克拉维(来自棒状链球菌)是一种与某些抗生素(如阿莫西林)联合使用的药物,通过不可逆的β-内酰胺酶抑制来阻断和或削弱某些细菌抵抗机制。目前正在开发的新型抗感染药包括瓜地诺明(来自链霉菌属,K01-0509),[37]是一种阻断革兰氏阴性菌第三型分泌系统的化合物。
阿维链霉菌是是目前应用最广泛的防治线虫和节肢动物感染的药物之一。
链霉菌产生用于其他医学治疗的化合物不太常见:米格拉斯特汀(来自钝顶链球菌)和博莱霉素(来自轮枝链球菌)是抗肿瘤(抗癌)药物;硼霉素(来自抗生素链球菌)显示出抗HIV-1病毒株的抗病毒活性以及抗菌活性。星形孢菌素(来自星形孢霉属)也具有从抗真菌到抗肿瘤的一系列活性(通过抑制蛋白激酶)。吸水链霉菌和绿色链霉菌产生天然双丙氨磷除草剂。
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