Lee Ying-Chiang Jeffrey, Javdan Bahar
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Biodes Res. 2023 Nov 2;5:0024. doi: 10.34133/bdr.0024. eCollection 2023.
The golden age has passed for antibiotic discovery, and while some antibiotics are currently in various phases of clinical trials in the United States, many pharmaceutical companies have abandoned antibiotic research. With the need for antibiotics, we should expand our horizon for therapeutic mining and can look toward understudied sources such as ice cores. Ice cores contain microorganisms and genetic material that have been frozen in time for thousands of years. The antibiotics used by these organisms are encoded in their genomes, which can be unlocked, identified, and characterized with modern advances in molecular biology, genetic sequencing, various computational approaches, and established natural product discovery pipelines. While synthetic biology can be used in natural product discovery approaches, synthetic biology and bioengineering efforts can also be leveraged in the selection and biodesign of increased compound yields, potency, and stability. Here, we provide the perspective that ice cores can be a source of novel antibiotic compounds and that the tools of synthetic biology can be used to design better antimicrobials.
抗生素发现的黄金时代已经过去，虽然目前在美国有一些抗生素正处于临床试验的不同阶段，但许多制药公司已经放弃了抗生素研究。鉴于对抗生素的需求，我们应该拓宽治疗性挖掘的视野，可以将目光投向研究较少的来源，比如冰芯。冰芯含有已经被冻结数千年的微生物和遗传物质。这些生物体所使用的抗生素编码在它们的基因组中，借助分子生物学、基因测序、各种计算方法以及成熟的天然产物发现流程等现代技术进展，可以解开这些编码、进行识别并加以表征。虽然合成生物学可用于天然产物发现方法，但合成生物学和生物工程方面的努力也可用于提高化合物产量、效力和稳定性的筛选及生物设计。在此，我们提出这样的观点：冰芯可以成为新型抗生素化合物的来源，并且合成生物学工具可用于设计更好的抗菌药物。
