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Artificial Biosynthetic Pathway for an Unnatural Terpenoid with an Iridiumcontaining P450

preprint
submitted on 17.03.2020 and posted on 18.03.2020 by Jing Huang, Zhennan Liu, brandon bloomer, Douglas Clark, Aindrila Mukhopadhyay, Jay Keasling, John Hartwig
Synthetic biology enables microbial hosts to produce complex molecules that are
otherwise produced by organisms that are rare or difficult to cultivate, but the structures of these
molecules are limited to chemical reactions catalyzed by natural enzymes. The integration of
artificial metalloenzymes (ArMs) that catalyze abiotic reactions into metabolic networks could
broaden the cache of molecules produced biosynthetically by microorgansms. We report the
assembly of an ArM containing an iridium-porphyrin complex in the cytoplasm of a terpene
producing Escherichia coli by a heterologous heme transport machinery, and insertion of this ArM
into a natural biosynthetic pathway to produce an unnatural terpenoid. This work shows that
synthetic biology and synthetic chemistry, incorporated together in whole cells, can produce
molecules previously inaccessible to nature.

Funding

DE-AC01-05CH11231

History

Email Address of Submitting Author

jhartwig@berkeley.edu

Institution

University of California, Berkeley

Country

United States

ORCID For Submitting Author

0000-0002-4157-468X

Declaration of Conflict of Interest

A provisional patent application has been submitted

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