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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

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Front. Chem. Sci. Eng.    2017, Vol. 11 Issue (1) : 37-45    https://doi.org/10.1007/s11705-017-1618-2
REVIEW ARTICLE
Genome reprogramming for synthetic biology
Kylie Standage-Beier1,Xiao Wang2()
1. School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA
2. School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287, USA
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Abstract

The ability to go from a digitized DNA sequence to a predictable biological function is central to synthetic biology. Genome engineering tools facilitate rewriting and implementation of engineered DNA sequences. Recent development of new programmable tools to reengineer genomes has spurred myriad advances in synthetic biology. Tools such as clustered regularly interspace short palindromic repeats enable RNA-guided rational redesign of organisms and implementation of synthetic gene systems. New directed evolution methods generate organisms with radically restructured genomes. These restructured organisms have useful new phenotypes for biotechnology, such as bacteriophage resistance and increased genetic stability. Advanced DNA synthesis and assembly methods have also enabled the construction of fully synthetic organisms, such as J. Craig Venter Institute (JCVI)-syn 3.0. Here we summarize the recent advances in programmable genome engineering tools.
Keywords CRISPR      genome engineering      synthetic biology      rational design     
Corresponding Author(s): Xiao Wang   
Just Accepted Date: 03 January 2017   Online First Date: 15 February 2017    Issue Date: 17 March 2017
 Cite this article:   
Kylie Standage-Beier,Xiao Wang. Genome reprogramming for synthetic biology[J]. Front. Chem. Sci. Eng., 2017, 11(1): 37-45.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-017-1618-2
https://academic.hep.com.cn/fcse/EN/Y2017/V11/I1/37
Fig.1  Programmable editing of genomes. (a) A schematic of CRISPR-directed targeting with wildtype S. pyogenes Cas9. Cas9 (blue) is targeted to a DNA sequence based on the presence of a protospacer adjacent motif (PAM, red) nucleotides matching those in a short guide RNA (sgRNA). The target DNA sequence is written beneath. The strand matching the 20 nucleotide guide of the sgRNA is orange and the complementary strand is black; (b) CRISPR-guided double stranded DNA breaks (DSBs) involving a recombination template have various modalities. DSBs either induce host homology directed repair (HDR) or DSBs kill cells that have not acquired the desired edit, wherein the full CRISPR target site is not present in the desired edit. HDR-mediated editing can be either a function of one or both of these modalities; (c) novel mutant versions of Cas9 that mediate single-stranded DNA cleavage have been developed to target recombination in a broad range of organisms
Fig.2  Large-scale reengineering of organisms. (a) Genome reduction methods, such as methods employing CRE recombinase, lambda Red recombineering, and CRISPR-nickases, have enabled large-scale reductions to the E. coli genome. Genome reduction methods look to investigate the emergent phenotypes by removal of large numbers of non-essential genes. These methods may identify novel organisms and phenotypes for synthetic biology; (b) multiplex automated genome engineering (MAGE) offers itself as a powerful tool for coupling DNA synthesis, targeted editing, and evolution. MAGE functions as an iterative process. Recoding oligo nucleotides are electroporated into E. coli, which are then screened for a desired phenotype. This process is repeated to maximize output from a biosynthetic pathway or to systematically replace DNA sequences (Adapted from [47]); (c) Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) is a promising tool for investigated evolution and combinatorial genetics. loxP sites (blue squares) are placed around genes (various color rectangles), induction of Cre recombinases leads to recombination between loxP sites resulting in deletions, inversions, duplications, and translocations. Resulting clones from this method can be screened for desired phenotypes; (d) Forward genome construction methods such as yeast assembly enabled construction of large-subgenomic fragments. The efficiency of yeast homologous recombination enables connection of multiple fragments. Homolgoue fragments are connected via yeast HDR to a bacterial artificial chromosome (BAC, orange) and yeast artificial chromosome (YAC, blue) sequence. These circular fragments can measure up to 1 megabase and be propagated in S. cerevisiae. These assemblies can be transferred to recipient organisms via various methods
Method Host Description Product Ref
MAGE Escherichia coli Multiplex automated genome engineering: an automated recombineering work flow for directed evolution Lycopene [47]
CAGE Escherichia coli Conjugative assembly genome engineering for hierarchical assembly of genomic mutations UAG codon replacement a) [52]
RAGE Escherichia coli Recombinase assisted genome engineering for integration of heterologous pathways into the E. coli genome Ethanol from brown macroalgae [63]
CRISPR/lambda Red Escherichia coli Integration of large synthetic constructs into the E. coli genome Isobutanol [32]
CasEMBLR Saccharomyces cerevisiae Multiplex assembly of biosynthetic pathways on the yeast genome Carotenoids and tyrosine [44]
mCRISTAR Saccharomyces cerevisiae Combined CRISPR and TAR cloning for construction and refactoring of pathways for application in heterologous organisms Tetarimycin A [74]
Tab.1  Example applications of genome engineering to obtain certain products
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