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Step-by-step optimization of a heterologous pathway for de novo naringenin production in Escherichia coli
by
Rodrigues, Joana L.
, Rodrigues, Ligia R.
, Gomes, Daniela
in
4-Coumarate-CoA ligase
/ Acid production
/ Acyltransferases - genetics
/ Acyltransferases - metabolism
/ Alfalfa
/ Ammonia
/ Ammonia-Lyases - genetics
/ Ammonia-Lyases - metabolism
/ antioxidants
/ Arabidopsis thaliana
/ biochemical pathways
/ Biomedical and Life Sciences
/ Biosynthetic Pathways - genetics
/ Biotechnological Products and Process Engineering
/ Biotechnology
/ chalcone
/ Chalcone isomerase
/ Chalcone synthase
/ Coenzyme A Ligases - genetics
/ Coenzyme A Ligases - metabolism
/ coumarate-CoA ligase
/ Coumaric Acids - metabolism
/ Cucurbita
/ E coli
/ Escherichia coli
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Flavanones - biosynthesis
/ Flavanones - metabolism
/ Flavobacterium johnsoniae
/ Genes
/ Genetic aspects
/ Identification and classification
/ Intramolecular Lyases - genetics
/ Intramolecular Lyases - metabolism
/ Life Sciences
/ Medicago sativa
/ Metabolic Engineering - methods
/ Microbial Genetics and Genomics
/ Microbiology
/ Microorganisms
/ Naringenin
/ naringenin-chalcone synthase
/ Optimization
/ p-Coumaric acid
/ Polyphenols
/ Properties
/ Tyrosine
/ Tyrosine - metabolism
/ tyrosine ammonia-lyase
2024
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Step-by-step optimization of a heterologous pathway for de novo naringenin production in Escherichia coli
by
Rodrigues, Joana L.
, Rodrigues, Ligia R.
, Gomes, Daniela
in
4-Coumarate-CoA ligase
/ Acid production
/ Acyltransferases - genetics
/ Acyltransferases - metabolism
/ Alfalfa
/ Ammonia
/ Ammonia-Lyases - genetics
/ Ammonia-Lyases - metabolism
/ antioxidants
/ Arabidopsis thaliana
/ biochemical pathways
/ Biomedical and Life Sciences
/ Biosynthetic Pathways - genetics
/ Biotechnological Products and Process Engineering
/ Biotechnology
/ chalcone
/ Chalcone isomerase
/ Chalcone synthase
/ Coenzyme A Ligases - genetics
/ Coenzyme A Ligases - metabolism
/ coumarate-CoA ligase
/ Coumaric Acids - metabolism
/ Cucurbita
/ E coli
/ Escherichia coli
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Flavanones - biosynthesis
/ Flavanones - metabolism
/ Flavobacterium johnsoniae
/ Genes
/ Genetic aspects
/ Identification and classification
/ Intramolecular Lyases - genetics
/ Intramolecular Lyases - metabolism
/ Life Sciences
/ Medicago sativa
/ Metabolic Engineering - methods
/ Microbial Genetics and Genomics
/ Microbiology
/ Microorganisms
/ Naringenin
/ naringenin-chalcone synthase
/ Optimization
/ p-Coumaric acid
/ Polyphenols
/ Properties
/ Tyrosine
/ Tyrosine - metabolism
/ tyrosine ammonia-lyase
2024
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Step-by-step optimization of a heterologous pathway for de novo naringenin production in Escherichia coli
by
Rodrigues, Joana L.
, Rodrigues, Ligia R.
, Gomes, Daniela
in
4-Coumarate-CoA ligase
/ Acid production
/ Acyltransferases - genetics
/ Acyltransferases - metabolism
/ Alfalfa
/ Ammonia
/ Ammonia-Lyases - genetics
/ Ammonia-Lyases - metabolism
/ antioxidants
/ Arabidopsis thaliana
/ biochemical pathways
/ Biomedical and Life Sciences
/ Biosynthetic Pathways - genetics
/ Biotechnological Products and Process Engineering
/ Biotechnology
/ chalcone
/ Chalcone isomerase
/ Chalcone synthase
/ Coenzyme A Ligases - genetics
/ Coenzyme A Ligases - metabolism
/ coumarate-CoA ligase
/ Coumaric Acids - metabolism
/ Cucurbita
/ E coli
/ Escherichia coli
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Flavanones - biosynthesis
/ Flavanones - metabolism
/ Flavobacterium johnsoniae
/ Genes
/ Genetic aspects
/ Identification and classification
/ Intramolecular Lyases - genetics
/ Intramolecular Lyases - metabolism
/ Life Sciences
/ Medicago sativa
/ Metabolic Engineering - methods
/ Microbial Genetics and Genomics
/ Microbiology
/ Microorganisms
/ Naringenin
/ naringenin-chalcone synthase
/ Optimization
/ p-Coumaric acid
/ Polyphenols
/ Properties
/ Tyrosine
/ Tyrosine - metabolism
/ tyrosine ammonia-lyase
2024
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Step-by-step optimization of a heterologous pathway for de novo naringenin production in Escherichia coli
Journal Article
Step-by-step optimization of a heterologous pathway for de novo naringenin production in Escherichia coli
2024
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Overview
Naringenin is a plant polyphenol, widely explored due to its interesting biological activities, namely anticancer, antioxidant, and anti-inflammatory. Due to its potential applications and attempt to overcome the industrial demand, there has been an increased interest in its heterologous production. The microbial biosynthetic pathway to produce naringenin is composed of tyrosine ammonia-lyase (TAL), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), and chalcone isomerase (CHI). Herein, we targeted the efficient de novo production of naringenin in
Escherichia coli
by performing a step-by-step validation and optimization of the pathway. For that purpose, we first started by expressing two TAL genes from different sources in three different
E. coli
strains. The highest
p
-coumaric acid production (2.54 g/L) was obtained in the tyrosine-overproducing M-PAR-121 strain carrying TAL from
Flavobacterium johnsoniae
(
FjT
AL). Afterwards, this platform strain was used to express different combinations of 4CL and CHS genes from different sources. The highest naringenin chalcone production (560.2 mg/L) was achieved by expressing
Fj
TAL combined with 4CL from
Arabidopsis thaliana
(
At
4CL) and CHS from
Cucurbita maxima
(
Cm
CHS). Finally, different CHIs were tested and validated, and 765.9 mg/L of naringenin was produced by expressing CHI from
Medicago sativa
(
Ms
CHI) combined with the other previously chosen genes. To our knowledge, this titer corresponds to the highest de novo production of naringenin reported so far in
E. coli
.
Key points
• Best enzyme and strain combination were selected for de novo naringenin production.
• After genetic and operational optimizations, 765.9 mg/L of naringenin was produced.
• This de novo production is the highest reported so far in E. coli.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
/ Acyltransferases - metabolism
/ Alfalfa
/ Ammonia
/ Biomedical and Life Sciences
/ Biosynthetic Pathways - genetics
/ Biotechnological Products and Process Engineering
/ chalcone
/ Coenzyme A Ligases - genetics
/ Coenzyme A Ligases - metabolism
/ E coli
/ Escherichia coli - metabolism
/ Genes
/ Identification and classification
/ Intramolecular Lyases - genetics
/ Intramolecular Lyases - metabolism
/ Metabolic Engineering - methods
/ Microbial Genetics and Genomics
/ naringenin-chalcone synthase
/ Tyrosine
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