Functional biology and biotechnology of thermophilic viruses.
Functional biology and biotechnology of thermophilic viruses.
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DOI：
10.1042/ebc20220209
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发表时间：
2023-08-11
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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病毒已经发展出复杂的生化和遗传机制来操纵和利用它们的宿主。从分子生物学的第一天起，来自病毒的酶就一直是必不可少的研究工具。然而，大多数已经商业化的病毒酶都来源于少量培养的病毒，考虑到宏基因组分析揭示的病毒的非凡多样性和丰富性，这是值得注意的。在过去的40年里，从嗜热原核生物中获得的新酶试剂激增，从嗜热病毒中获得的酶试剂应该是同样有效的工具。本文综述了嗜热病毒的功能生物学和生物技术，重点是DNA聚合酶，连接酶，内溶素和外壳蛋白。对来自栖热菌属、水生植物科和硝化菌属的细菌的DNA聚合酶和引物聚合酶的功能分析揭示了具有强校对和逆转录酶能力的酶的新分支。嗜热RNA连接酶1同源物的特征在于来自Rhodothermus和栖热菌，两者都商业化用于单链模板的环化。来自感染栖热菌属（Thermus）、亚栖热菌属（Meiothermus）和土芽孢杆菌属（Geobacillus）的细菌的内溶素已经显示出针对革兰氏阴性和革兰氏阳性细菌的高稳定性和异常广泛的裂解活性，使它们成为作为抗微生物剂商业化的目标。嗜热病毒感染硫化叶菌属和栖热菌属菌株的外壳蛋白已被表征，具有作为分子穿梭的多种潜在应用。为了衡量这些蛋白质未开发资源的规模，我们还记录了来自高温环境的未培养病毒基因组编码的20，000多个基因，这些基因编码DNA聚合酶，连接酶，内溶素或外壳蛋白结构域。
Viruses have developed sophisticated biochemical and genetic mechanisms to manipulate and exploit their hosts. Enzymes derived from viruses have been essential research tools since the first days of molecular biology. However, most viral enzymes that have been commercialized are derived from a small number of cultivated viruses, which is remarkable considering the extraordinary diversity and abundance of viruses revealed by metagenomic analysis. Given the explosion of new enzymatic reagents derived from thermophilic prokaryotes over the past 40 years, those obtained from thermophilic viruses should be equally potent tools. This review discusses the still-limited state of the art regarding the functional biology and biotechnology of thermophilic viruses with a focus on DNA polymerases, ligases, endolysins, and coat proteins. Functional analysis of DNA polymerases and primase-polymerases from phages infecting Thermus, Aquificaceae, and Nitratiruptor has revealed new clades of enzymes with strong proofreading and reverse transcriptase capabilities. Thermophilic RNA ligase 1 homologs have been characterized from Rhodothermus and Thermus phages, with both commercialized for circularization of single-stranded templates. Endolysins from phages infecting Thermus, Meiothermus, and Geobacillus have shown high stability and unusually broad lytic activity against Gram-negative and Gram-positive bacteria, making them targets for commercialization as antimicrobials. Coat proteins from thermophilic viruses infecting Sulfolobales and Thermus strains have been characterized, with diverse potential applications as molecular shuttles. To gauge the scale of untapped resources for these proteins, we also document over 20,000 genes encoded by uncultivated viral genomes from high-temperature environments that encode DNA polymerase, ligase, endolysin, or coat protein domains.