Schmidt Markus, Pei Lei, Budisa Nediljko
Biofaction KG, Kundmanngasse 39/12, Vienna, 1030, Austria.
AK Biokatalyse, Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Straße 10, 10623, Berlin, Germany.
Adv Biochem Eng Biotechnol. 2018;162:301-315. doi: 10.1007/10_2016_14.
The basic chemical constitution of all living organisms in the context of carbon-based chemistry consists of a limited number of small molecules and polymers. Until the twenty-first century, biology was mainly an analytical science and has now reached a point where it merges with engineering science, paving the way for synthetic biology. One of the objectives of synthetic biology is to try to change the chemical compositions of living cells, that is, to create an artificial biological diversity, which in turn fosters a new sub-field of synthetic biology, xenobiology. In particular, the genetic code in living systems is based on highly standardized chemistry composed of the same "letters" or nucleotides as informational polymers (DNA, RNA) and the 20 amino acids which serve as basic building blocks for proteins. The universality of the genetic code enables not only vertical gene transfer within the same species but also horizontal gene transfer across biological taxa, which require a high degree of standardization and interconnectivity. Although some minor alterations of the standard genetic code are found in nature (e.g., proteins containing non-conical amino acids exist in nature, and some organisms use alternated coding systems), all structurally deep chemistry changes within living systems are generally lethal, making the creation of artificial biological system an extremely difficult challenge.In this context, one of the great challenges for bioscience is the development of a strategy for expanding the standard basic chemical repertoire of living cells. Attempts to alter the meaning of the genetic information stored in DNA as an informational polymer by changing the chemistry of the polymer (i.e., xeno-nucleic acids) or by changes in the genetic code have already yielded successful results. In the future this should enable the partial or full redirection of the biological information flow to generate "new" version(s) of the genetic code derived from the "old" biological world.In addition to the scientific challenges, the attempt to increase biochemical diversity also raises important ethical and philosophical issues. Although promotors of this branch of synthetic biology highlight the many potential applications to come (e.g., novel tools for diagnostics and fighting infection diseases), such developments could also bring risks affecting social, political, and other structures of nearly all societies.
在基于碳的化学背景下，所有生物的基本化学组成都由有限数量的小分子和聚合物构成。直到21世纪，生物学主要还是一门分析科学，如今已发展到与工程科学融合的阶段，为合成生物学铺平了道路。合成生物学的目标之一是尝试改变活细胞的化学组成，即创造一种人工生物多样性，这反过来又催生出合成生物学的一个新分支——异生物学。特别是，生命系统中的遗传密码基于高度标准化的化学过程，由与信息聚合物（DNA、RNA）相同的“字母”或核苷酸以及作为蛋白质基本构建单元的20种氨基酸组成。遗传密码的通用性不仅使得同一物种内能够进行垂直基因转移，还能实现跨生物分类群的水平基因转移，这需要高度的标准化和相互连接性。尽管在自然界中发现了一些标准遗传密码的微小改变（例如，自然界中存在含非标准氨基酸的蛋白质，一些生物体使用交替编码系统），但生命系统内所有结构上深度的化学变化通常都是致命的，这使得创建人工生物系统成为一项极其艰巨的挑战。在这种背景下，生物科学面临的重大挑战之一是制定一种策略来扩展活细胞的标准基本化学组成。通过改变聚合物的化学性质（即异源核酸）或改变遗传密码来改变存储在DNA作为信息聚合物中的遗传信息的含义的尝试已经取得了成功。未来，这应该能够使生物信息流部分或完全重新定向，以产生源自“旧”生物世界的遗传密码的“新”版本。除了科学挑战之外，增加生化多样性的尝试还引发了重要的伦理和哲学问题。尽管合成生物学这一分支的推动者强调了许多即将出现的潜在应用（例如，用于诊断和对抗传染病的新型工具），但这样的发展也可能带来影响几乎所有社会的社会、政治和其他结构的风险。
