Acevedo-Rocha Carlos G, Budisa Nediljko
Biosyntia ApS, 2970, Hørsholm, Denmark.
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2970, Hørsholm, Denmark.
Microb Biotechnol. 2016 Sep;9(5):666-76. doi: 10.1111/1751-7915.12398. Epub 2016 Aug 4.
Biology is an analytical and informational science that is becoming increasingly dependent on chemical synthesis. One example is the high-throughput and low-cost synthesis of DNA, which is a foundation for the research field of synthetic biology (SB). The aim of SB is to provide biotechnological solutions to health, energy and environmental issues as well as unsustainable manufacturing processes in the frame of naturally existing chemical building blocks. Xenobiology (XB) goes a step further by implementing non-natural building blocks in living cells. In this context, genetic code engineering respectively enables the re-design of genes/genomes and proteins/proteomes with non-canonical nucleic (XNAs) and amino (ncAAs) acids. Besides studying information flow and evolutionary innovation in living systems, XB allows the development of new-to-nature therapeutic proteins/peptides, new biocatalysts for potential applications in synthetic organic chemistry and biocontainment strategies for enhanced biosafety. In this perspective, we provide a brief history and evolution of the genetic code in the context of XB. We then discuss the latest efforts and challenges ahead for engineering the genetic code with focus on substitutions and additions of ncAAs as well as standard amino acid reductions. Finally, we present a roadmap for the directed evolution of artificial microbes for emancipating rare sense codons that could be used to introduce novel building blocks. The development of such xenomicroorganisms endowed with a 'genetic firewall' will also allow to study and understand the relation between code evolution and horizontal gene transfer.
生物学是一门分析性和信息性科学，且越来越依赖于化学合成。一个例子是DNA的高通量低成本合成，这是合成生物学（SB）研究领域的基础。SB的目标是在天然存在的化学构件框架内，为健康、能源和环境问题以及不可持续的制造过程提供生物技术解决方案。异生生物学（XB）通过在活细胞中引入非天然构件更进一步。在这种背景下，遗传密码工程分别能够用非经典核酸（XNA）和氨基酸（非天然氨基酸）重新设计基因/基因组以及蛋白质/蛋白质组。除了研究生命系统中的信息流和进化创新外，XB还允许开发新型的治疗性蛋白质/肽、用于合成有机化学潜在应用的新型生物催化剂以及增强生物安全性的生物遏制策略。从这个角度出发，我们简要介绍了XB背景下遗传密码的历史和演变。然后，我们讨论了遗传密码工程的最新进展和面临的挑战，重点是对非天然氨基酸的替换和添加以及标准氨基酸的减少。最后，我们提出了一个定向进化人工微生物以释放稀有义密码子的路线图，这些密码子可用于引入新型构件。这种具有“基因防火墙”的异微生物的开发也将有助于研究和理解密码进化与水平基因转移之间的关系。
