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The Translational Coupling of Daidzein Reductase and Dihydrodaidzein Racemase Genes Improves the Production of Equol and Its Analogous Derivatives in Engineered Lactic Acid Bacteria

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Equol (EQ) and its analogous derivatives 5-hydroxy-equol (5-OH-EQ) and 5-hydroxy-dehydroequol (5-OH-D-EQ) are isoflavones which benefit human health. They are produced from daidzein and genistein, respectively, in the gut by microorganisms harboring the genes daidzein reductase ( dzr ), dihydrodaidzein racemase ( ifc A), dihydrodaidzein reductase ( ddr ) and tetrahydrodaidzein reductase ( tdr ). Since the production of these isoflavones is of interest due to their great-health benefits for humans, the heterologous expression of dzr, ddr, tdr and ifc A from Slackia isoflavoniconvertenes DSM 22006T in lactic acid bacteria (LAB) was used as a strategy to produce EQ, 5-OH-EQ and 5-OH-D-EQ in soy beverages. However, efficient production of these compounds was only demonstrated in two engineered Limosilactobacillus fermentum strains, and it is dependent on dihydrodaidzein racemase (DDRC). In order to increase the production of EQ and its analogous derivatives in different LAB species and genera, different strategies were performed with the ifc A gene. Translational coupling of ifc A and dzr genes (pNZ:TuR.dzr.ifcA) under the influence of a constitutive promoter improved the efficiency of production of EQ, 5-OH-EQ and 5-OH-D-EQ in the engineered LAB strains. The translational coupling of ifc A and dzr genes allowed the production of high concentrations of eq (111.15 ± 9.20–410.56 ± 24.15 μM), 5-OH-eq (71.00 ± 4.25 μM–148.22 ± 9.15 μM) and 5-OH-D-eq (111.15 ± 9.20–201.09 ± 7.65 μM) in soy beverages by different engineered LAB genera, such as L. fermentum INIA 584L, Lactilactobacillus plantarum WCFS1, and Lactocaseibacillus paracasei BL23. Translational coupling has allowed engineered Laboratories strains belonging to different genera, such as L. fermentum, L. plantarum, and L. paracasei, to produce high concentrations of EQ, 5-OH-EQ and 5-OH-D-EQ. Translational coupling could be exploited as a strategy for the efficient production of bioactive compounds.

Source: ACS Synthetic Biology

DOI: 10.1021/acssynbio.5c00532

Authors: Susana Langa, José Antonio Curiel, Ángela Peirotén, José María Landete

Institution: Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria

Language: English

Topic: Probiotics and Fermented Foods

Subfield: Food Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Zero hunger

Open Access status: hybrid

Estimated APC paid: $4,500