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利用遗传密码工程对微生物进行合成异化:为何以及如何实现?

Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?

作者信息

Kubyshkin Vladimir, Budisa Nediljko

机构信息

Biocatalysis group, Institute of Chemistry, Technical University of Berlin, Germany.

出版信息

Biotechnol J. 2017 Aug;12(8). doi: 10.1002/biot.201600097. Epub 2017 Jul 3.

DOI:10.1002/biot.201600097
PMID:28671771
Abstract

The main goal of synthetic biology (SB) is the creation of biodiversity applicable for biotechnological needs, while xenobiology (XB) aims to expand the framework of natural chemistries with the non-natural building blocks in living cells to accomplish artificial biodiversity. Protein and proteome engineering, which overcome limitation of the canonical amino acid repertoire of 20 (+2) prescribed by the genetic code by using non-canonic amino acids (ncAAs), is one of the main focuses of XB research. Ideally, estranging the genetic code from its current form via systematic introduction of ncAAs should enable the development of bio-containment mechanisms in synthetic cells potentially endowing them with a "genetic firewall" i.e. orthogonality which prevents genetic information transfer to natural systems. Despite rapid progress over the past two decades, it is not yet possible to completely alienate an organism that would use and maintain different genetic code associations permanently. In order to engineer robust bio-contained life forms, the chemical logic behind the amino acid repertoire establishment should be considered. Starting from recent proposal of Hartman and Smith about the genetic code establishment in the RNA world, here the authors mapped possible biotechnological invasion points for engineering of bio-contained synthetic cells equipped with non-canonical functionalities.

摘要

合成生物学(SB)的主要目标是创造适用于生物技术需求的生物多样性,而异生生物学(XB)旨在利用活细胞中的非天然构建块扩展天然化学的框架,以实现人工生物多样性。蛋白质和蛋白质组工程通过使用非标准氨基酸(ncAA)克服了遗传密码规定的20种(+2)标准氨基酸库的限制,是XB研究的主要重点之一。理想情况下,通过系统引入ncAA使遗传密码与其当前形式相疏离,应该能够在合成细胞中开发生物遏制机制,从而可能赋予它们一个“基因防火墙”,即防止遗传信息转移到自然系统的正交性。尽管在过去二十年中取得了快速进展,但要永久性地完全分离出一种使用并维持不同遗传密码关联的生物体仍然是不可能的。为了构建强大的生物遏制生命形式,应该考虑氨基酸库建立背后的化学逻辑。从哈特曼和史密斯最近关于RNA世界中遗传密码建立的提议出发,本文作者绘制了配备非标准功能的生物遏制合成细胞工程可能的生物技术入侵点。

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