CF-Targeter: A Rational Biological Cell Factory Targeting Platform for Biosynthetic Target Chemicals

Biosynthesis
is a promising method for chemical synthesis. However,
due to varieties between different microorganism hosts, yield and
heterologous pathways needed for production of target chemical may
also vary from different strains. One of the main challenges in metabolic
engineering is to select an appropriate chassis host for specified
target chemical production. However, with thousands of microorganisms
existing in nature and extremely complicated metabolism within them,
it is still time-consuming and error-prone work to achieve such a
goal only through experimental methods, even with some existing computational
methods. Hence, more efficient methods should be proposed to assist
in selecting appropriate chassis hosts. In this article, based on
symbolic reaction repositories and a pathway search algorithm which
performed 1 400 000 searches for per target compound,
we established a biological reasoning system for appropriate chassis
host selection by coupling with various GEM-models. By using a supercomputer
to calculate the biosynthetic pathways for more than 1 month, nearly
50 000 000 biosynthetic pathways are computed for production
of 6026 compounds within 70 microorganisms. With retrieved organisms
for specified target production, several heterologous biosynthetic
pathways can be shown in length order, and then the maximum theoretical
yields and thermodynamic feasibility can be calculated in real time
under customized growth conditions and physiological states. From
the computation results, the system not only identifies experimentally
validated pathways but also outputs more efficient solutions with
less heterologous steps or higher maximum possible theoretical yield
by engineering other organism hosts. CF-targeter is available at http://www.rxnfinder.org/cf_targeter/