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De novo production of prenylnaringenin compounds by a metabolically engineered ...

Gomes, Daniela Filipa Correia; Rodrigues, Joana Lúcia Lima Correia; Scrutton, Nigel S.; Rodrigues, L. R.

Prenylnaringenin (PN) compounds, namely 8-prenylnaringenin (8-PN), 3-prenylnaringenin (3-PN), and 6-prenylnaringenin (6-PN), are reported to have several interesting bioactivities. This study aimed to validate a biosynthetic pathway for de novo production of PN in Escherichia coli. A previously optimized E. coli chassis capable of efficiently de novo producing naringenin was used to evaluate eleven prenyltransf...


De novo production of xanthohumol by a metabolically engineered Escherichia coli

Gomes, Daniela Filipa Correia; Santos, Joana; Venâncio, Armando; Rodrigues, Joana Lúcia Lima Correia; Scrutton, Nigel S.; Rodrigues, L. R.

Xanthohumol is a prenylflavonoid from hops with relevant bioactivities. Microbial production has emerged as a sustainable and potentially economic solution to produce it. Herein, we constructed a pathway for the de novo production of xanthohumol in Escherichia coli. Since the xanthohumol pathway depends on the availability of dimethylallyl pyrophosphate (DMAPP) and S-adenosylmethionine (SAM), SAM synthase (metK...


CRISPR-Cas12a-driven engineering of DMAPP and SAM pathways in E. coli for de no...

Gomes, Daniela Filipa Correia; Rodrigues, Joana Lúcia Lima Correia; Scrutton, Nigel S.; Rodrigues, L. R.

Prenylflavonoids, including xanthohumol and prenylnaringenin (PN) (3-PN, 6-PN, and 8-PN), have been reported as bioactive compounds. However, their low accumulation in plants limits its broader utilization. We engineered Escherichia coli strains for the de novo biosynthesis of PNs and xanthohumol. Stepwise optimization was performed to construct naringenin chalcone and naringenin pathways. E. coli M-PAR-121 exp...


Exploiting CRISPR-Cas12a to engineer DMAPP/SAM pathways in Escherichia coli tow...

Gomes, Daniela Filipa Correia; Rodrigues, Joana Lúcia Lima Correia; Scrutton, Nigel S.; Rodrigues, L. R.

Prenylflavonoids are flavonoid derived compounds with interesting bioactivities, namely estrogenic and anticancer. Among them, xanthohumol and prenylnaringenin (PN) isomers, including 3-prenylnaringenin (3-PN), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN) have attracted special interest. Due to their low production and accumulation in plants, the construction of microbial cell factories able to prod...


Exploiting synthetic biology for the production of prenylflavonoids in Escheric...

Gomes, Daniela Filipa Correia; Rodrigues, Joana Lúcia Lima Correia; Scrutton, Nigel S.; Rodrigues, L. R.

Prenylflavonoids are flavonoids bearing a prenylated sidechain. Among them, xanthohumol and prenylnaringenin (PN) isomers, including 3-prenylnaringenin (3-PN), 6-prenylnaringenin (6-PN), and 8-prenylnaringenin (8-PN) have attracted interest due to their bioactive properties. However, their low accumulation in plants limits their utilization. The construction of microbial cell factories able to produce them appe...


CRISPR-Cas12a system as a tool to construct boosted DMAPP-Escherichia coli stra...

Gomes, Daniela Filipa Correia; Rodrigues, Joana Lúcia Lima Correia; Scrutton, Nigel S.; Rodrigues, L. R.

Prenylflavonoids are flavonoid derived compounds with interesting bioactivities, namely estrogenic and anticancer. This study aimed to design and validate a biosynthetic pathway to de novo produce prenylnaringenins (PNs) in Escherichia coli. Firstly, tyrosine ammonia-lyase, 4-coumarate-CoA ligase, chalcone synthase, and chalcone isomerase were expressed to produce the intermediate naringenin in high amounts (68...


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