Biosynthesis of plant hemostatic dencichine in Escherichia coli

Wenna Li, Zhao Zhou, Xianglai Li, Lin Ma, Qingyuan Guan, Guojun Zheng, Hao Liang, Yajun Yan, Xiaolin Shen, Jia Wang, Xinxiao Sun () and Qipeng Yuan ()
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Wenna Li: Beijing University of Chemical Technology
Zhao Zhou: Beijing University of Chemical Technology
Xianglai Li: Beijing University of Chemical Technology
Lin Ma: Beijing University of Chemical Technology
Qingyuan Guan: Beijing University of Chemical Technology
Guojun Zheng: Beijing University of Chemical Technology
Hao Liang: Beijing University of Chemical Technology
Yajun Yan: The University of Georgia
Xiaolin Shen: Beijing University of Chemical Technology
Jia Wang: Beijing University of Chemical Technology
Xinxiao Sun: Beijing University of Chemical Technology
Qipeng Yuan: Beijing University of Chemical Technology

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract Dencichine is a plant-derived nature product that has found various pharmacological applications. Currently, its natural biosynthetic pathway is still elusive, posing challenge to its heterologous biosynthesis. In this work, we design artificial pathways through retro-biosynthesis approaches and achieve de novo production of dencichine. First, biosynthesis of the two direct precursors L−2, 3-diaminopropionate and oxalyl-CoA is achieved by screening and integrating microbial enzymes. Second, the solubility of dencichine synthase, which is the last and only plant-derived pathway enzyme, is significantly improved by introducing 28 synonymous rare codons into the codon-optimized gene to slow down its translation rate. Last, the metabolic network is systematically engineered to direct the carbon flux to dencichine production, and the final titer reaches 1.29 g L−1 with a yield of 0.28 g g−1 glycerol. This work lays the foundation for sustainable production of dencichine and represents an example of how synthetic biology can be harnessed to generate unnatural pathways to produce a desired molecule.

Date: 2022
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DOI: 10.1038/s41467-022-33255-3

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