Literature DB >> 28280154

Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond.

Leslie A Mitchell1,2, Ann Wang3,4, Giovanni Stracquadanio3,5,6, Zheng Kuang1,2, Xuya Wang1,2, Kun Yang3,5, Sarah Richardson3,5, J Andrew Martin1,2, Yu Zhao1,2, Roy Walker7, Yisha Luo7, Hongjiu Dai8, Kang Dong8, Zuojian Tang1,2, Yanling Yang9, Yizhi Cai7, Adriana Heguy10, Beatrix Ueberheide1,9, David Fenyö1,2, Junbiao Dai4, Joel S Bader3,4, Jef D Boeke11,2.   

Abstract

We describe design, rapid assembly, and characterization of synthetic yeast Sc2.0 chromosome VI (synVI). A mitochondrial defect in the synVI strain mapped to synonymous coding changes within PRE4 (YFR050C), encoding an essential proteasome subunit; Sc2.0 coding changes reduced Pre4 protein accumulation by half. Completing Sc2.0 specifies consolidation of 16 synthetic chromosomes into a single strain. We investigated phenotypic, transcriptional, and proteomewide consequences of Sc2.0 chromosome consolidation in poly-synthetic strains. Another "bug" was discovered through proteomic analysis, associated with alteration of the HIS2 transcription start due to transfer RNA deletion and loxPsym site insertion. Despite extensive genetic alterations across 6% of the genome, no major global changes were detected in the poly-synthetic strain "omics" analyses. This work sets the stage for completion of a designer, synthetic eukaryotic genome.
Copyright © 2017, American Association for the Advancement of Science.

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Year:  2017        PMID: 28280154     DOI: 10.1126/science.aaf4831

Source DB:  PubMed          Journal:  Science        ISSN: 0036-8075            Impact factor:   47.728


  61 in total

1.  Synthetic Biology: Building a custom eukaryotic genome de novo.

Authors:  Darren J Burgess
Journal:  Nat Rev Genet       Date:  2017-04-12       Impact factor: 53.242

2.  A spring collection of designer yeast chromosomes.

Authors:  Katarzyna Marcinkiewicz
Journal:  Nat Biotechnol       Date:  2017-06-07       Impact factor: 54.908

3.  Karyotype engineering by chromosome fusion leads to reproductive isolation in yeast.

Authors:  Jingchuan Luo; Xiaoji Sun; Brendan P Cormack; Jef D Boeke
Journal:  Nature       Date:  2018-08-01       Impact factor: 49.962

Review 4.  Controlling the Implementation of Transgenic Microbes: Are We Ready for What Synthetic Biology Has to Offer?

Authors:  Finn Stirling; Pamela A Silver
Journal:  Mol Cell       Date:  2020-05-21       Impact factor: 17.970

5.  Synthetic genome engineering gets infectious.

Authors:  Leslie A Mitchell; Tom Ellis
Journal:  Proc Natl Acad Sci U S A       Date:  2017-10-09       Impact factor: 11.205

6.  Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods.

Authors:  Lauren M Oldfield; Peter Grzesik; Alexander A Voorhies; Nina Alperovich; Derek MacMath; Claudia D Najera; Diya Sabrina Chandra; Sanjana Prasad; Vladimir N Noskov; Michael G Montague; Robert M Friedman; Prashant J Desai; Sanjay Vashee
Journal:  Proc Natl Acad Sci U S A       Date:  2017-09-19       Impact factor: 11.205

Review 7.  The unique kind of human artificial chromosome: Bypassing the requirement for repetitive centromere DNA.

Authors:  Craig W Gambogi; Jennine M Dawicki-McKenna; Glennis A Logsdon; Ben E Black
Journal:  Exp Cell Res       Date:  2020-04-01       Impact factor: 3.905

8.  Beyond editing to writing large genomes.

Authors:  Raj Chari; George M Church
Journal:  Nat Rev Genet       Date:  2017-08-30       Impact factor: 53.242

9.  3D organization of synthetic and scrambled chromosomes.

Authors:  Guillaume Mercy; Julien Mozziconacci; Vittore F Scolari; Kun Yang; Guanghou Zhao; Agnès Thierry; Yisha Luo; Leslie A Mitchell; Michael Shen; Yue Shen; Roy Walker; Weimin Zhang; Yi Wu; Ze-Xiong Xie; Zhouqing Luo; Yizhi Cai; Junbiao Dai; Huanming Yang; Ying-Jin Yuan; Jef D Boeke; Joel S Bader; Héloïse Muller; Romain Koszul
Journal:  Science       Date:  2017-03-10       Impact factor: 47.728

10.  The Future of Multiplexed Eukaryotic Genome Engineering.

Authors:  David B Thompson; Soufiane Aboulhouda; Eriona Hysolli; Cory J Smith; Stan Wang; Oscar Castanon; George M Church
Journal:  ACS Chem Biol       Date:  2017-12-28       Impact factor: 5.100

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