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Rebuilding microbial genomes
Author(s) -
Holt Robert A.,
Warren Rene,
Flibotte Stephane,
Missirlis Perseus I.,
Smailus Duane E.
Publication year - 2007
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.20585
Subject(s) - genome , biology , gene , synthetic biology , computational biology , dna , genetics
Engineered microbes are of great potential utility in biotechnology and basic research. In principle, a cell can be built from scratch by assembling small molecule sets with auto‐catalytic properties. Alternatively, DNA can be isolated or directly synthesized and molded into a synthetic genome using existing genomic blueprints and molecular biology tools. Activating such a synthetic genome will yield a synthetic cell. Here we examine obstacles associated with this latter approach using a model system whereby a donor genome from H. influenzae is fragmented, and the pieces are then modified and reassembled stepwise in an E. coli host cell. There are obstacles associated with this strategy related to DNA transfer, DNA replication, cross‐talk in gene regulation and compatibility of gene products between donor and host. Encouragingly, analysis of gene expression indicates widespread transcription of H. influenzae genes in E. coli , and analysis of gap locations in H. influenzae and other microbial genome assemblies reveals few genes routinely incompatible with E. coli . In conclusion, rebuilding and booting a genome remains a feasible and pragmatic approach to creating a synthetic microbial cell. BioEssays 29:580–590, 2007. © 2007 Wiley Periodicals, Inc.