Promiscuous enzymatic activity-aided multiple-pathway network design for metabolic flux rearrangement in hydroxytyrosol biosynthesis

Nature Communications
Wei ChenShuang-Yan Tang

Abstract

Genetic diversity is a result of evolution, enabling multiple ways for one particular physiological activity. Here, we introduce this strategy into bioengineering. We design two hydroxytyrosol biosynthetic pathways using tyrosine as substrate. We show that the synthetic capacity is significantly improved when two pathways work simultaneously comparing to each individual pathway. Next, we engineer flavin-dependent monooxygenase HpaBC for tyrosol hydroxylase, tyramine hydroxylase, and promiscuous hydroxylase active on both tyrosol and tyramine using directed divergent evolution strategy. Then, the mutant HpaBCs are employed to catalyze two missing steps in the hydroxytyrosol biosynthetic pathways designed above. Our results demonstrate that the promiscuous tyrosol/tyramine hydroxylase can minimize the cell metabolic burden induced by protein overexpression and allow the biosynthetic carbon flow to be divided between two pathways. Thus, the efficiency of the hydroxytyrosol biosynthesis is significantly improved by rearranging the metabolic flux among multiple pathways.

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Citations

Jun 4, 2019·Chembiochem : a European Journal of Chemical Biology·Yifan DengMarc Fontecave
Jun 10, 2019·Applied Microbiology and Biotechnology·James BrittonKevin E O'Connor
Nov 12, 2019·Biotechnology for Biofuels·Xue LiuGuang-Rong Zhao
Oct 18, 2020·Applied Microbiology and Biotechnology·Xu TanJing Wu
Jul 9, 2021·Journal of Agricultural and Food Chemistry·Fu-Xing NiuJian-Zhong Liu
Sep 17, 2021·Journal of Agricultural and Food Chemistry·Bixia FuJifeng Yuan
Sep 30, 2021·Chemical Communications : Chem Comm·Yi ZhouUwe T Bornscheuer

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Methods Mentioned

BETA
glycosylation
PCR
electrophoresis

Software Mentioned

Autodock Vina
Gromacs
Modeler
Excel
Modeller
Coot

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