Biology Reference
In-Depth Information
FUTURE PERSPECTIVES OF BGM SYSTEMS ACCRUED FROM
THE PRESENT ACHIEVEMENTS
Current technological barriers in handling between genes and genomes will be lowered or
removed in 10 years. Pipelines of certain modifications on existing genomes and innovation
of general chassis will be expected. In 20 years, guest genomes would be gradually expanded
from: (1) existing beneficial microbial genomes for further modification to those of (2)
VNC (Viable Not Culturable) microbes in natural environments; (3) large-sized modified
DNA to be delivered to unicellular eukaryotes, algae, or fungi, and higher multicellular
eukaryotes such as mammals or plants; and (4) designed ones in silico for basic researches
and future applications.
(1) Designed microbes based on existing ones should be of great use for basic research and
industrial applications. Purpose-oriented genomes can be organized and produced without
the need of template DNA if whole nucleotide sequence information is available.
(2) VNC microbes are considered major inhabitants in natural environments and therefore
tremendous untouched guest genome resources.
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Once their complete genome sequences
are determined by, for example, metagenomic procedures,
59,60
they are prospectively
constructed starting from chemical oligomers which would lead to unprecedented
challenges. By seeking the reason why they do not grow in laboratory conditions, and
investigating how to convert them to be culturable in the laboratory, those huge natural
resources presently unnoticed are desired for future wider and unpredicted applications in
various fields of life sciences.
(3) Genome delivery technology should not be limited to the case of bacteria microbes.
Handling protocols for microbial guest genomes described in this chapter are readily
applied to far-larger parts of mammal and plant genomes than ever. The large DNA would
dramatically require improved protocols in the delivery process and create target regions
previously thought to be very hard. Although we do not draw concrete pipelines and time
schedules on this issue, once the DNA size limit is cleared, applications should be open to
any cell types.
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(4) Genome is the ultimate molecule manipulation which reorganizes and regulates global
cellular activities. De novo genome design should be a combined task of a number of on-
going cutting-edge technologies in various areas. Our strategy starting from bottoming-up
gene clusters illustrated in
Figure 12.6
is one of many approaches. Guest genomes
synthesized with perfect match to the blueprint made in silico should provide initial kick-
off strain only. Evolutionary ideas and selection methods should be included at certain
stages to produce desired ones more rapidly.
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SUMMARY
Recent next generation genome-sequencing technologies are being applied to an unlimited
number of species on the Earth, which provides various directions of research and
applications in synthetic biology.
2,7,61
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In contrast, full engineering of genomes even from
bacteria, far smaller than those of higher eukaryotes, are very limited. The state-of-the-art
technology remains immature for a wide range of applications due to the difficulty of daily
handling and high cost of producing correct genomes. Genome synthesis/cloning
technologies discussed in this chapter have proven that entire bacterial genomes and even
the smallest eukaryote genome,
S. cerevisiae
, can be synthesized from DNA oligomers.
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De
novo
synthesis of functional genomes from scratch, frequently mentioned as the ultimate
motivation of genome synthesis, remains the greatest challenge for the future. The rational
design of bacterial genomes requires rational sequence-writing disciplines to draw complete
nucleotide sequences. Practical and solid bacterial genome design for applications and
