{"id":3522,"date":"2019-05-16T17:41:14","date_gmt":"2019-05-16T08:41:14","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=3522"},"modified":"2019-05-17T14:25:35","modified_gmt":"2019-05-17T05:25:35","slug":"total-synthesis-of-escherichia-coli-with-a-recoded-genome","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3522","title":{"rendered":"Total synthesis of Escherichia coli with a recoded genome &#038; Scientists Created Bacteria With a Synthetic Genome. Is This Artificial Life?"},"content":{"rendered":"<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p id=\"Abs1\" class=\"js-section-title section-title strong position-relative tighten-line-height background-gray-light pt20 pb6 pl0 pr20 standard-space-below small-space-above mq640-pt10 mq640-pb10 mq640-pl20 mq640-mt0 mq640-ml-20 mq640-mr-20 extend-left\"><strong>Abstract<\/strong><\/p>\n<div id=\"Abs1-content\" class=\"pl20 mq875-pl0 js-collapsible-section\">\n<p>&nbsp;<\/p>\n<p>Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon\u2014out of up to 6 synonyms\u2014to encode each amino acid. Synonymous codon choice has diverse and important roles, and many synonymous substitutions are detrimental. Here we demonstrate that the number of codons used to encode the canonical amino acids can be reduced, through the genome-wide substitution of target codons by defined synonyms. We create a variant of\u00a0<i>Escherichia coli<\/i>\u00a0with a four-megabase synthetic genome through a high-fidelity convergent total synthesis. Our synthetic genome implements a defined recoding and refactoring scheme\u2014with simple corrections at just seven positions\u2014to replace every known occurrence of two sense codons and a stop codon in the genome. Thus, we recode 18,214 codons to create an organism with a 61-codon genome; this organism uses 59 codons to encode the 20 amino acids, and enables the deletion of a previously essential transfer RNA.<\/p>\n<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1192-5?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h4 class=\"article-item__title serif\">Construction of an\u00a0<i>Escherichia coli<\/i>\u00a0genome with fewer codons sets records<\/h4>\n<p>&nbsp;<\/p>\n<h5>The biggest synthetic genome so far has been made, with a smaller set of amino-acid-encoding codons than usual \u2014 raising the prospect of encoding proteins that contain unnatural amino-acid residues.<\/h5>\n<div class=\"article__aside align-right hide-print\">\n<div class=\"pdf__download shrink--aside\"><\/div>\n<\/div>\n<div class=\"align-left\">\n<div class=\"article__body serif cleared\">\n<p>Over the past decade, decreases in the costs of chemically synthesizing DNA and improved methods for assembling DNA fragments have enabled researchers to scale up synthetic biology to the level of generating entire chromosomes and genomes. So far, synthetic DNA has been constructed with up to one million base pairs, notably a set of chromosomes from the yeast\u00a0<i>Saccharomyces cerevisiae<\/i>\u00a0and several versions of the genome of the bacterium\u00a0<i>Mycoplasma mycoides<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">1<\/a><\/sup><sup>,<\/sup><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR2\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">2<\/a><\/sup>. Now,\u00a0<a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1192-5\" data-track=\"click\" data-label=\"https:\/\/www.nature.com\/articles\/s41586-019-1192-5\" data-track-category=\"body text link\">writing in\u00a0<i>Nature<\/i><\/a>, Fredens\u00a0<i>et al.<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR3\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">3<\/a><\/sup>\u00a0report the completion of a 4-million-base-pair synthetic version of the\u00a0<i>Escherichia coli<\/i>\u00a0genome. This is a landmark in the emerging field of synthetic genomics, and finally applies the technology to the laboratory\u2019s workhorse bacterium.<\/p>\n<p>&nbsp;<\/p>\n<aside class=\"recommended pull pull--left sans-serif\" data-label=\"Related\"><a href=\"https:\/\/www.nature.com\/articles\/s41586-019-1192-5\" data-track=\"click\" data-track-label=\"recommended article\"><img decoding=\"async\" class=\"recommended__image\" src=\"https:\/\/media.nature.com\/w400\/magazine-assets\/d41586-019-01584-x\/d41586-019-01584-x_16728242.jpg\" \/><\/a><\/p>\n<p class=\"recommended__title serif\">Read the paper: Total synthesis of Escherichia coli with a recoded genome<\/p>\n<\/aside>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>Synthetic genomics offers a new way of understanding the rules of life, while at the same time moving synthetic biology towards a future in which genomes can be written to design. The pioneers in the field \u2014 the researchers at the J. Craig Venter Institute in Rockville, Maryland \u2014 have used this method to better define the minimal set of genes required for a free-living cell. By adopting an approach that involves redesigning genome segments by computer, chemically synthesizing the fragments and then assembling them, these pioneers succeeded<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR2\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">2<\/a><\/sup>\u00a0in reducing the size of the\u00a0<i>M. mycoides<\/i>genome by around 50%. Doing the same with just genome-editing tools would be much more laborious, as past work with\u00a0<i>E. coli<\/i>\u00a0demonstrates: here, gene-deletion methods have removed, at best, only 15% of the genome<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR4\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">4<\/a><\/sup>.<\/p>\n<p>Fredens and colleagues used this reduced genome from\u00a0<i>E. coli<\/i>\u00a0as the template for a synthetic genome with another kind of minimization in mind \u2014 codon reduction. The genetic code has inherent redundancy: there are 64 codons (triplets of \u2018letters\u2019, or bases) to encode just 20 amino acids plus the \u2018start\u2019 and \u2018stop\u2019 points that mark the beginning and end of a stretch of protein-coding sequence. This redundancy means, for example, that there are six codons that encode the amino acid serine, and three possible stop codons. Through design, synthesis and assembly, Fredens\u00a0<i>et al.<\/i><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR3\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">3<\/a><\/sup>\u00a0have been able to construct an\u00a0<i>E. coli\u00a0<\/i>genome that uses only 61 of the 64 available codons in its protein-coding sequences, replacing two serine codons and one stop codon with synonyms (codons that are \u2018spelt\u2019 differently but give the same instruction). Past work using genome-editing tools has already produced a synthetic\u00a0<i>E. coli<\/i>\u00a0that uses just 63 of the 64 codons, but this required only the stop codons with the sequence TAG (of which there were just 321 around the genome) to be changed to an alternative stop codon<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR5\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">5<\/a><\/sup>. Reduction to 61 codons demanded that a whopping 18,214 codons be changed, necessitating a genome-synthesis approach.<\/p>\n<p>Fredens and colleagues built their synthetic\u00a0<i>E. coli\u00a0<\/i>genome by using large-scale DNA-assembly and genome-integration methods that they had developed previously<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR6\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">6<\/a><\/sup>\u00a0to probe the limits of codon changes in\u00a0<i>E. coli<\/i>. In their approach (Fig. 1), DNA is computationally designed, chemically synthesized and assembled in 100-kilobase fragments in vectors in\u00a0<i>S. cerevisiae<\/i>; these vectors are then taken up by\u00a0<i>E. coli\u00a0<\/i>and integrated into the genome in the direct place of the equivalent natural region. Iterating this process five times resulted in 500-kilobase sections of DNA being replaced by synthetic versions. Eight strains of\u00a0<i>E. coli\u00a0<\/i>were produced in this way, each harbouring synthetic DNA sections that covered a different region of the genome. These sections were then combined using conjugation methods to make the complete synthetic genome.<\/p>\n<p>&nbsp;<\/p>\n<figure class=\"figure\">\n<div class=\"embed intensity--high\">\n<div class=\"embed intensity--high\"><img decoding=\"async\" class=\"figure__image\" src=\"https:\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-01584-x\/d41586-019-01584-x_16728312.jpg\" alt=\"\" data-src=\"\/\/media.nature.com\/w800\/magazine-assets\/d41586-019-01584-x\/d41586-019-01584-x_16728312.jpg\" \/><\/div>\n<\/div><figcaption>\n<p class=\"figure__caption sans-serif\"><span class=\"mr10\"><b>Figure 1 | Design and construction of a recoded genome.<\/b>\u00a0<b>a<\/b>, Fredens\u00a0<i>et al<\/i>.<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR3\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">3<\/a><\/sup>\u00a0recoded three base triplets (codons) \u2014 TCG and TCA, which encode the amino acid serine, and TAG, a stop codon that marks the end of a protein-coding sequence \u2014 to alternatives that have the same functions (AGC, AGT and TAA respectively) in the genome of the bacterium\u00a0<i>Escherichia coli<\/i>.\u00a0<b>b<\/b>, In some genomic locations, open reading frames (ORFs; protein-coding regions) overlap, and a change in the codons of one ORF might produce an unwanted change in the overlapping region. Fredens\u00a0<i>et al.<\/i>\u00a0\u2018refactored\u2019 these ORFs to separate them, as illustrated for ORF1 and ORF2 (the two ORFs on the left are \u2018read\u2019 in the same direction; the two on the right are read in opposite directions).\u00a0<b>c<\/b>, Redesigned DNA was synthesized and assembled into 100-kilobase fragments in the yeast\u00a0<i>Saccharomyces cerevisiae<\/i>; fragments were then combined into sections and integrated into the\u00a0<i>E. coli<\/i>genome. The sections were brought together to generate the complete functional synthetic genome.<\/span><\/p>\n<\/figcaption><\/figure>\n<p>The large-scale construction was impressively successful, with very low off-target mutation rates, but was not without its challenges. Many genes in the\u00a0<i>E. coli<\/i>\u00a0genome partially overlap with others, and in 91 cases the overlapping regions contained codons that needed to be changed. This is complex because synonymous alterations in one protein-coding sequence might alter the amino acids encoded by the overlapping one. To tackle this, the team \u2018refactored\u2019 79 locations in the genome, duplicating the sequence to separate out overlapped coding sequences into individual recoded ones (Fig. 1). Although this approach was generally successful, it did require careful debugging in a few cases in which refactoring also altered gene regulation.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>The final strain proved viable and was able to grow in a range of typical laboratory conditions, albeit a little less vigorously than its natural counterpart. It no longer uses the stop codon TAG or the two serine codons TCG and TCA, so the cellular machinery that recognizes these can now be either deleted or reassigned to recruit \u2018non-canonical\u2019 amino acids beyond the usual 20 used by most living cells. Such recruitment has already been shown to be useful in the 63-codon\u00a0<i>E. coli<\/i>, both for biotechnology projects, in which non-canonical amino acids are encoded into desired sequence positions to provide residues that can take part in chemical reactions that natural proteins can\u2019t; and for biosafety reasons, in that the natural transfer of readable DNA-encoded information in and out of the synthetic\u00a0<i>E. coli<\/i>\u00a0is limited because the cell operates with a slightly different genetic code from the rest of the natural world<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR5\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">5<\/a><\/sup>. Expect all of these applications to be expanded in the new 61-codon\u00a0<i>E. coli<\/i>, which has the potential to encode the use of more than one non-canonical amino acid, and to generate a more stringent genetic firewall (because 3 of the 64 codons are no longer recognized).<\/p>\n<p>Synthesis of a 4-million-base-pair genome and reduction of the genetic code to 61 codons are new records for synthetic genomics, but might not be for much longer. The international Sc2.0 consortium is closing in on synthesizing all 16 chromosomes of the 12-million-base-pair\u00a0<i>S. cerevisiae<\/i>\u00a0genome \u2014 the first synthetic genome of a eukaryotic organism, the group that includes plants, animals and fungi \u2014 and the synthesis of a 57-codon\u00a0<i>E. coli<\/i>\u00a0genome is also under way<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR1\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">1<\/a><\/sup><sup>,<\/sup><sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR7\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">7<\/a><\/sup>. A genome of the bacterium\u00a0<i>Salmonella<\/i>\u00a0Typhimurium that has two fewer codons than the natural organism is also being constructed<sup><a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29#ref-CR8\" data-track=\"click\" data-action=\"anchor-link\" data-track-label=\"go to reference\" data-track-category=\"references\">8<\/a><\/sup>. This could one day enable bacteria with synthetic genomes to be used as cell-based technologies in the human gut.<\/p>\n<p>From a technological standpoint, the most interesting aspect of all these different projects is that the workflows for synthetic-genome construction are remarkably similar, with kilobase sections of synthesized DNA being assembled (by the process of homologous recombination) into 50- to 100-kilobase pieces in yeast cells, and these pieces then being used to replace natural sequences inside the target organism (by selectable recombination methods). Standardization of methods will enable steps to be automated and more research groups to enter the field. Genome minimization and codon reduction are just the first uses of this new technology, which could one day give us functionally reorganized genomes and genomes that are custom designed to direct cells to perform specialized tasks.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<p><span class=\"emphasis\">Nature<\/span>\u00a0<strong>569<\/strong>, 492-494 (2019)<\/p>\n<p>&nbsp;<\/p>\n<div class=\"emphasis\">doi: 10.1038\/d41586-019-01584-x<\/div>\n<\/div>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nature.com\/articles\/d41586-019-01584-x?utm_source=feedburner&amp;utm_medium=feed&amp;utm_campaign=Feed%3A+nature%2Frss%2Fcurrent+%28Nature+-+Issue%29\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<div class=\"css-1vkm6nb ehdk2mb0\">\n<h4 id=\"link-278bf36e\" class=\"css-1s4ffep e1h9rw200\"><span class=\"balancedHeadline\">Scientists Created Bacteria With a Synthetic Genome. Is This Artificial Life?<\/span><\/h4>\n<\/div>\n<p>&nbsp;<\/p>\n<h5 class=\"css-1ifw933 e1wiw3jv0\">In a milestone for synthetic biology, colonies of E. coli thrive with DNA constructed from scratch by humans, not nature.<\/h5>\n<p>&nbsp;<\/p>\n<p><img decoding=\"async\" class=\"css-11cwn6f\" style=\"color: #737373; font-size: 1rem;\" src=\"https:\/\/static01.nyt.com\/images\/2019\/05\/21\/science\/15SCI-GENOME2\/15SCI-GENOME2-articleLarge.jpg?quality=75&amp;auto=webp&amp;disable=upscale\" sizes=\"((min-width: 600px) and (max-width: 1004px)) 84vw, (min-width: 1005px) 60vw, 100vw\" srcset=\"https:\/\/static01.nyt.com\/images\/2019\/05\/21\/science\/15SCI-GENOME2\/15SCI-GENOME2-articleLarge.jpg?quality=90&amp;auto=webp 600w,https:\/\/static01.nyt.com\/images\/2019\/05\/21\/science\/15SCI-GENOME2\/15SCI-GENOME2-jumbo.jpg?quality=90&amp;auto=webp 1024w,https:\/\/static01.nyt.com\/images\/2019\/05\/21\/science\/15SCI-GENOME2\/15SCI-GENOME2-superJumbo.jpg?quality=90&amp;auto=webp 2048w\" alt=\"\" \/><\/p>\n<div>\n<header class=\"css-llk6mt euiyums4\">\n<div class=\"css-79elbk\" data-testid=\"photoviewer-wrapper\">\n<div class=\"css-1a48zt4 ehw59r15\" data-testid=\"photoviewer-children\">\n<figure class=\"sizeMedium layoutHorizontal css-1ox9jel toneNews\" role=\"group\" aria-label=\"media\"><figcaption class=\"css-17ai7jg emkp2hg0\"><span class=\"css-8i9d0s e13ogyst0\">A colored scanning electron micrograph of the bacteria E. coli. Scientists in Britain created bacteria with \u201crecoded\u201d DNA.\u00a0<\/span><span class=\"emkp2hg2 css-1nwzsjy e1z0qqy90\"><span class=\"emkp2hg2 css-1nwzsjy e1z0qqy90\"><span class=\"css-1ly73wi e1tej78p0\">Credit<\/span><span class=\"css-1dv1kvn\">Credit<\/span>Nano Creative\/Science Source<\/span><\/span>&nbsp;<\/p>\n<\/figcaption><\/figure>\n<\/div>\n<\/div>\n<\/header>\n<\/div>\n<section class=\"meteredContent css-1i2y565\">\n<div class=\"css-1fanzo5 StoryBodyCompanionColumn\">\n<div class=\"css-53u6y8\">\n<p class=\"css-1ygdjhk evys1bk0\">Scientists have created a living organism whose DNA is entirely human-made\u00a0\u2014 perhaps a new form of life, experts said, and a milestone in the field of synthetic biology.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Researchers at the Medical Research Council Laboratory of Molecular Biology in Britain reported on Wednesday that they had rewritten the DNA of the bacteria Escherichia coli, fashioning a synthetic genome four times larger and far more complex than any previously created.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">The bacteria are alive, though unusually shaped and reproducing slowly. But their cells operate according to a new set of biological rules, producing familiar proteins with a reconstructed genetic code.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">The achievement one day may lead to organisms that produce novel medicines or other valuable molecules, as living factories. These synthetic bacteria also may offer clues as to how the genetic code arose in the early history of life.<\/p>\n<\/div>\n<aside class=\"css-17l9gfh\"><\/aside>\n<\/div>\n<div id=\"story-ad-1-wrapper\" class=\"css-1r07izm\">\n<div id=\"story-ad-1-slug\" class=\"css-l9onyx\">\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<div class=\"css-1fanzo5 StoryBodyCompanionColumn\">\n<div class=\"css-53u6y8\">\n<p class=\"css-1ygdjhk evys1bk0\">\u201cIt\u2019s a landmark,\u201d said Tom Ellis, director of the Center for Synthetic Biology at Imperial College London, who was not involved in the new study. \u201cNo one\u2019s done anything like it in terms of size or in terms of number of changes before.\u201d<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Each gene in a living genome is detailed in an alphabet of four bases, molecules called adenine, thymine, guanine and cytosine (often described only by their first letters: A, T, G, C). A gene may be made of thousands of bases.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Genes direct cells to choose among 20 amino acids, the building blocks of proteins, the workhorses of every cell. Proteins carry out a vast number of jobs in the body, from ferrying oxygen in the blood to generating force in our muscles.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Nine years ago, researchers\u00a0<a class=\"css-1g7m0tk\" title=\"\" href=\"https:\/\/www.nytimes.com\/2010\/05\/21\/science\/21cell.html?module=inline\">built a synthetic genome that was one million base pairs long<\/a>. The new E. coli genome, reported in the journal Nature,\u00a0<a class=\"css-1g7m0tk\" title=\"\" href=\"https:\/\/www.nature.com\/articles\/s41586-019-1192-5\" target=\"_blank\" rel=\"noopener noreferrer\">is four million base pairs\u00a0<\/a>long and had to be constructed with entirely new methods.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">The new study was led by Jason Chin, a molecular biologist at the M.R.C. laboratory, who wanted to understand why all living things encode genetic information in the same baffling way.<\/p>\n<\/div>\n<aside class=\"css-o6xoe7\">\n<div class=\"css-j64t31\"><\/div>\n<\/aside>\n<\/div>\n<div class=\"css-1fanzo5 StoryBodyCompanionColumn\">\n<div class=\"css-53u6y8\">\n<p>&nbsp;<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">The production of each amino acid in the cell is directed by three bases arranged in the DNA strand. Each of these trios is known as a codon. The codon TCT, for example, ensures that an amino acid called serine is attached to the end of a new protein.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Since there are only 20 amino acids, you\u2019d think the genome only needs 20 codons to make them. But the genetic code is full of redundancies, for reasons that no one understands.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Amino acids are encoded by\u00a061\u00a0codons, not 20. Production of serine, for example, is governed by six different codons. (Another three codons are called stop codons; they tell DNA where to stop construction of an amino acid.)<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Like many scientists, Dr. Chin was intrigued by all this duplication. Were all these chunks of DNA essential to life?<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">\u201cBecause life universally uses 64 codons, we really didn\u2019t have an answer,\u201d Dr. Chin said. So he set out to create an organism that could shed some light on the question.<\/p>\n<\/div>\n<aside class=\"css-o6xoe7\">\n<div class=\"css-ke163a\" data-testid=\"article-companion-wrapper\">\n<div id=\"newsletter-module\" class=\"css-48vsi0\">\n<div class=\"css-1k9ek97\">\n<div class=\"css-1hdd06o\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/aside>\n<\/div>\n<div class=\"css-79elbk\" data-testid=\"photoviewer-wrapper\">\n<div class=\"css-z3e15g\" data-testid=\"photoviewer-wrapper-hidden\">\n<p>&nbsp;<\/p>\n<\/div>\n<div class=\"css-hebz1t ehw59r12\" data-testid=\"photoviewer-children\">\n<div class=\"css-t972an ehw59r13\" data-testid=\"photoviewer-overlay\">\n<div class=\"css-1letflc ehw59r11\" data-testid=\"photoviewer-captionblock\"><\/div>\n<div class=\"css-1hxcymq ehw59r14\">\n<div class=\"css-8h527k\">\n<div data-testid=\"lazyimage-container\">\n<p><img decoding=\"async\" class=\"css-1j5kxti e1t57l6r0\" src=\"https:\/\/static01.nyt.com\/images\/2019\/05\/15\/science\/15SCI-GENOME\/15SCI-GENOME-articleLarge.jpg?quality=75&amp;auto=webp&amp;disable=upscale\" sizes=\"((min-width: 600px) and (max-width: 1004px)) 84vw, (min-width: 1005px) 60vw, 100vw\" srcset=\"https:\/\/static01.nyt.com\/images\/2019\/05\/15\/science\/15SCI-GENOME\/15SCI-GENOME-articleLarge.jpg?quality=90&amp;auto=webp 600w,https:\/\/static01.nyt.com\/images\/2019\/05\/15\/science\/15SCI-GENOME\/15SCI-GENOME-jumbo.jpg?quality=90&amp;auto=webp 1024w,https:\/\/static01.nyt.com\/images\/2019\/05\/15\/science\/15SCI-GENOME\/15SCI-GENOME-superJumbo.jpg?quality=90&amp;auto=webp 2048w\" alt=\"\" \/><span class=\"css-8i9d0s e13ogyst0\" style=\"color: #737373; font-size: 1rem;\">A colored scanning electronic micrograph of synthesized Mycoplasma mycoides, bacteria with a genome containing one million base pairs. Now scientists have created an E.coli genome four times larger. <\/span><span class=\"css-vuqh7u e1z0qqy90\" style=\"color: #737373; font-size: 1rem;\"><span class=\"css-1ly73wi e1tej78p0\">Credit<\/span>Thomas Deerinck, NCMIR\/Science Source<\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"css-1fanzo5 StoryBodyCompanionColumn\">\n<div class=\"css-53u6y8\">\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">After some preliminary experiments, he and his colleagues designed a modified version of the E. coli genome on a computer that only required 61 codons to produce all of the amino acids the organism needs.<\/p>\n<\/div>\n<aside class=\"css-o6xoe7\"><\/aside>\n<\/div>\n<div id=\"story-ad-3-wrapper\" class=\"css-2ninbb\">\n<div id=\"story-ad-3-slug\" class=\"css-l9onyx\"><span style=\"font-size: 1rem;\">\u00a0<\/span><\/div>\n<\/div>\n<div class=\"css-1fanzo5 StoryBodyCompanionColumn\">\n<div class=\"css-53u6y8\">\n<p class=\"css-1ygdjhk evys1bk0\">Instead of requiring six codons to make serine, this genome used just four. It had two stop codons, not three. In effect, the researchers treated E. coli DNA as if it were a gigantic text file, performing a search-and-replace function at over 18,000 spots.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Now the researchers had a blueprint for a new genome four million base pairs long. They could synthesize the DNA in a lab, but introducing it into the bacteria \u2014 essentially substituting synthetic genes for those made by evolution \u2014 was a daunting challenge.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">The genome was too long and too complicated to force into a cell in one attempt. Instead, the researchers built small segments and swapped them piece by piece into E. coli genomes. By the time they were done, no natural segments remained.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Much to their relief, the altered E. coli did not die. The bacteria grow more slowly than regular E. coli and develop longer, rod-shaped cells. But they are very much alive.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Dr. Chin hopes to build on this experiment by removing more codons and compressing the genetic code even further. He wants to see just how streamlined the genetic code can be while still supporting life.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">The Cambridge team is just one of many racing in recent years to build synthetic genomes. The list of potential uses is a long one. One attractive possibility: Viruses may not be able to invade recoded cells.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Many companies today use genetically engineered microbes to make medicines like insulin or useful chemicals like detergent enzymes. If a viral outbreak hits the fermentation tanks, the results can be catastrophic. A microbe with synthetic DNA might be made immune to such attacks.<\/p>\n<\/div>\n<aside class=\"css-o6xoe7\"><\/aside>\n<\/div>\n<div id=\"story-ad-4-wrapper\" class=\"css-1r07izm\">\n<div id=\"story-ad-4-slug\" class=\"css-l9onyx\"><\/div>\n<\/div>\n<div class=\"css-1fanzo5 StoryBodyCompanionColumn\">\n<div class=\"css-53u6y8\">\n<p>&nbsp;<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Recoding DNA could also allow scientists to program engineered cells so that their genes won\u2019t work if they escape into other species. \u201cIt creates a genetic firewall,\u201d said Finn Stirling, a synthetic biologist at Harvard Medical School who was not involved in the new study.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Researchers are also interested in recoding life because it opens up the opportunity to make molecules with entirely new kinds of chemistry.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">Beyond the 20 amino acids used by all living things, there are hundreds of other kinds. A compressed genetic code will free up codons that scientists can use to encode these new building blocks, making new proteins that carry out new tasks in the body.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">James Kuo, a postdoctoral researcher at Harvard Medical School, offered a note of caution. Tacking bases together to make genomes remains enormously costly.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">\u201cIt\u2019s just way too expensive for academic groups to keep pursuing,\u201d Dr. Kuo said.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">But E. coli is a workhorse of laboratory research, and now it\u2019s clear that its genome can be synthesized. It\u2019s not hard to imagine that prices will fall as demands for custom, synthetic DNA rise. Researchers could apply Dr. Chin\u2019s methods to yeast or other species.<\/p>\n<p class=\"css-1ygdjhk evys1bk0\">\u201cIn theory, you could recode anything,\u201d said Mr. Stirling.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(\uc6d0\ubb38: <a href=\"https:\/\/www.nytimes.com\/2019\/05\/15\/science\/synthetic-genome-bacteria.html\">\uc5ec\uae30<\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~)<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; &nbsp; Abstract &nbsp; Nature uses 64 codons to encode the synthesis of proteins from the genome, and chooses 1 sense codon\u2014out of up to<a href=\"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3522\" class=\"more-link\">(more&#8230;)<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[33,34,29,30],"tags":[],"class_list":["post-3522","post","type-post","status-publish","format-standard","hentry","category-do-biology","category-lets-do-chemistry","category-lets-do-science","category-recent-science-news"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":1223,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1223","url_meta":{"origin":3522,"position":0},"title":"Optimizing orthogonality","author":"biochemistry","date":"July 23, 2018","format":false,"excerpt":"\u00a0 \u00a0 (\uc6d0\ubb38) \u00a0 Nature Chemistry\u00a0volume\u00a010,\u00a0pages\u00a0802\u2013803\u00a0(2018) \u00a0 \u00a0 A new pyrrolysyl-tRNA synthetase\/PyltRNA (PylRS\/PyltRNA) pair that is mutually orthogonal to existing PylRS\/PyltRNA pairs has now been discovered and optimized. This system could enable the site-specific incorporation of a greater number of distinct non-conical amino acids into a protein. \u00a0 \u00a0 The\u2026","rel":"","context":"In &quot;Let's Do Chemistry!&quot;","block_context":{"text":"Let's Do Chemistry!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=34"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2985,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2985","url_meta":{"origin":3522,"position":1},"title":"How to make an organelle in eukaryotes","author":"biochemistry","date":"March 29, 2019","format":false,"excerpt":"\u00a0 \u00a0 A key step in the evolution of complex organisms like eukaryotes was the organization of specific tasks into organelles. Reinkemeier\u00a0et al.\u00a0designed an artificial, membraneless organelle into mammalian cells to perform orthogonal translation. In response to a specific codon in a selected messenger RNA, ribosomes confined to this organelle\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4207,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4207","url_meta":{"origin":3522,"position":2},"title":"The structure of DNA","author":"biochemistry","date":"October 11, 2019","format":false,"excerpt":"\u00a0 \u00a0 In the early 1950s, the identity of genetic material was still a matter of debate. The discovery of the helical structure of double-stranded DNA settled the matter \u2014 and changed biology forever. \u00a0 \u00a0 On 25 April 1953, James Watson and Francis Crick announced1\u00a0in\u00a0Nature\u00a0that they \u201cwish to suggest\u201d\u00a0a\u2026","rel":"","context":"In &quot;Essays on Science&quot;","block_context":{"text":"Essays on Science","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=32"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2672,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2672","url_meta":{"origin":3522,"position":3},"title":"CRISPR-Cas9-Based Genome Editing of Human Cells","author":"biochemistry","date":"February 15, 2019","format":false,"excerpt":"\u00a0 \u00a0 CRISPR\/Cas9 systems are engineered versions of the Cas9 protein and guide RNA. \u00a0Typically, they are identical to the\u00a0Streptococcus pyogenes\u00a0type II CRISPR systems, except that a single guide-RNA is used in place of the complementary crRNAs and tracrRNAs of the natural CRISPR system, and the Cas9 protein is codon-optimized\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"Genome Editing Overview2","src":"https:\/\/i0.wp.com\/sites.tufts.edu\/crispr\/files\/2014\/11\/Genome-Editing-Overview2-1024x667.png?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/sites.tufts.edu\/crispr\/files\/2014\/11\/Genome-Editing-Overview2-1024x667.png?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/sites.tufts.edu\/crispr\/files\/2014\/11\/Genome-Editing-Overview2-1024x667.png?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/sites.tufts.edu\/crispr\/files\/2014\/11\/Genome-Editing-Overview2-1024x667.png?resize=700%2C400&ssl=1 2x"},"classes":[]},{"id":3891,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3891","url_meta":{"origin":3522,"position":4},"title":"Inserting DNA with CRISPR","author":"biochemistry","date":"July 16, 2019","format":false,"excerpt":"\u00a0 \u00a0 Most prokaryotes rely on the CRISPR-Cas system for adaptive immunity against viruses and mobile elements (1,\u00a02). Small RNAs produced from CRISPR direct Cas effector proteins to seek and destroy nucleic acids from invaders that have complementary target sites (3). There are multiple types of CRISPR, which are defined\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2582,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2582","url_meta":{"origin":3522,"position":5},"title":"Technologies to watch in 2019","author":"biochemistry","date":"January 29, 2019","format":false,"excerpt":"\u00a0 \u00a0 From higher-resolution imaging to genome-sized DNA molecules built from scratch, the year ahead looks exciting for life-science technology. \u00a0 An automated bioreactor system for growing yeast, which can be used to investigate synthetic genomes \u2014 one area poised to make big strides this year.Credit: Tim Llewellyn\/Ginkgo Bioworks \u00a0\u2026","rel":"","context":"In &quot;Essays on Science&quot;","block_context":{"text":"Essays on Science","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=32"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_sharing_enabled":false,"jetpack_shortlink":"https:\/\/wp.me\/p9Xo1j-UO","_links":{"self":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/3522","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3522"}],"version-history":[{"count":4,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/3522\/revisions"}],"predecessor-version":[{"id":3538,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/3522\/revisions\/3538"}],"wp:attachment":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3522"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3522"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3522"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}