Bioorthogonal information storage in L-DNA with a high-fidelity mirror-image Pfu DNA polymerase
Bioorthogonal information storage in L-DNA with a high-fidelity mirror-image Pfu DNA polymerase
复制标题
DOI：
10.1038/s41587-021-00969-6
复制
发表时间：
2021-07-29
影响因子：
46.9
通讯作者：
Zhu, Ting F.
中科院分区：
文献类型：
--
作者：
Fan, Chuyao;Deng, Qiang;Zhu, Ting F.
天然DNA是精心进化来存储遗传信息的。手性反转的L-DNA，具有相同的信息能力，但耐生物降解，可以作为一个强大的，生物正交的信息库。在这里，我们化学合成一个90 kDa的高保真镜像Pfu DNA聚合酶，使一个酶大小的镜像基因的准确装配。我们使用聚合酶在L-DNA中编码Louis Pasteur在1860年的一段话，第一次提出了生物学的镜像世界。我们通过在D-DNA存储库中嵌入一个嵌合的D-DNA/L-DNA关键分子来实现手性隐写，该分子根据阅读的手性传递虚假或秘密的信息。此外，我们表明，微量的L-DNA条形码保存在水中从当地池塘仍然可扩增和测序1年，而在相同条件下的D-DNA条形码不能扩增后1天。这些下一代镜像分子工具可能会改变先进镜像生物学系统的发展，并为实现镜像中心法则及其应用探索铺平道路。
Natural DNA is exquisitely evolved to store genetic information. The chirally inverted L-DNA, possessing the same informational capacity but resistant to biodegradation, may serve as a robust, bioorthogonal information repository. Here we chemically synthesize a 90-kDa high-fidelity mirror-image Pfu DNA polymerase that enables accurate assembly of a kilobase-sized mirror-image gene. We use the polymerase to encode in L-DNA an 1860 paragraph by Louis Pasteur that first proposed a mirror-image world of biology. We realize chiral steganography by embedding a chimeric D-DNA/L-DNA key molecule in a D-DNA storage library, which conveys a false or secret message depending on the chirality of reading. Furthermore, we show that a trace amount of an L-DNA barcode preserved in water from a local pond remains amplifiable and sequenceable for 1 year, whereas a D-DNA barcode under the same conditions could not be amplified after 1 day. These next-generation mirror-image molecular tools may transform the development of advanced mirror-image biology systems and pave the way for the realization of the mirror-image central dogma and exploration of their applications.