8B3C

Chalcone synthase from Hordeum vulgare complexed with CoA and eriodictyol

Summary for 8B3C

• Entry DOI: 10.2210/pdb8b3c/pdb
• Descriptor: Chalcone synthase 2, (2S)-2-(3,4-DIHYDROXYPHENYL)-5,7-DIHYDROXY-2,3-DIHYDRO-4H-CHROMEN-4-ONE, COENZYME A, ... (4 entities in total)
• Functional Keywords: polyketide synthase, chalcone biosynthesis, transferase
• Biological source: Hordeum vulgare
• Total number of polymer chains: 2
• Total formula weight: 92585.29

Authors

Zhang, L.,Groves, M.R. (deposition date: 2022-09-16, release date: 2023-09-27, Last modification date: 2024-01-24)

Primary citation

Peng, B.,Zhang, L.,He, S.,Oerlemans, R.,Quax, W.J.,Groves, M.R.,Haslinger, K.
Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids.
J.Agric.Food Chem., 72:529-539, 2024

PubMed Abstract: Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from , in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.

PubMed: 38109879
DOI: 10.1021/acs.jafc.3c06785

Experimental method

X-RAY DIFFRACTION (2 Å)