Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | e70069 |
| Fachzeitschrift | Engineering in life sciences |
| Jahrgang | 26 |
| Ausgabenummer | 2 |
| Publikationsstatus | Veröffentlicht - 24 Feb. 2026 |
Abstract
Hesperetin is a bioactive flavonoid with potential applications in pharmaceuticals and nutraceuticals, yet its low natural abundance limits commercial use. In this study, a two-step whole-cell bioconversion process was developed for the microbial production of hesperetin from naringenin in Escherichia coli. The 4-hydroxyphenylacetate-3-hydroxylase enzyme complex (HpaBC) enabled cytochrome P450-independent conversion of naringenin to eriodictyol. Subsequent 4′-O-methylation was achieved using a plant-derived flavonoid 4'-O-methyltransferase (FOMT) coupled with a halide methyltransferase (HMT) for in situ S-adenosylmethionine (SAM) regeneration. Enzyme activity was first confirmed individually in vitro and in vivo, followed by integration into recombinant whole-cell systems, co-expressing all desired enzymes. Process optimization through delayed co-substrate addition, improving induction conditions, and machine learning-guided parameter selection increased hesperetin yields up to 70.6% with minimal byproduct formation. This work demonstrates the feasibility of combining process development and digital optimization strategies for the sustainable production of methylated flavonoids in microbial systems. The resulting E. coli platform provides a scalable blueprint for future biotechnological applications involving cofactor-dependent plant secondary metabolism.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Biotechnologie
- Umweltwissenschaften (insg.)
- Environmental engineering
- Chemische Verfahrenstechnik (insg.)
- Bioengineering
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in: Engineering in life sciences, Jahrgang 26, Nr. 2, e70069, 24.02.2026.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Optimized Bioconversion of Naringenin to Hesperetin in Escherichia coli With Halide Methyltransferase-Mediated S-Adenosylmethionine Regeneration
AU - Wildhagen, Maik
AU - Malke, Nina
AU - Wang, Qimin
AU - Zhuang, Xiaoying
AU - Beutel, Sascha
N1 - Publisher Copyright: © 2026 The Author(s). Engineering in Life Sciences published by Wiley-VCH GmbH.
PY - 2026/2/24
Y1 - 2026/2/24
N2 - Hesperetin is a bioactive flavonoid with potential applications in pharmaceuticals and nutraceuticals, yet its low natural abundance limits commercial use. In this study, a two-step whole-cell bioconversion process was developed for the microbial production of hesperetin from naringenin in Escherichia coli. The 4-hydroxyphenylacetate-3-hydroxylase enzyme complex (HpaBC) enabled cytochrome P450-independent conversion of naringenin to eriodictyol. Subsequent 4′-O-methylation was achieved using a plant-derived flavonoid 4'-O-methyltransferase (FOMT) coupled with a halide methyltransferase (HMT) for in situ S-adenosylmethionine (SAM) regeneration. Enzyme activity was first confirmed individually in vitro and in vivo, followed by integration into recombinant whole-cell systems, co-expressing all desired enzymes. Process optimization through delayed co-substrate addition, improving induction conditions, and machine learning-guided parameter selection increased hesperetin yields up to 70.6% with minimal byproduct formation. This work demonstrates the feasibility of combining process development and digital optimization strategies for the sustainable production of methylated flavonoids in microbial systems. The resulting E. coli platform provides a scalable blueprint for future biotechnological applications involving cofactor-dependent plant secondary metabolism.
AB - Hesperetin is a bioactive flavonoid with potential applications in pharmaceuticals and nutraceuticals, yet its low natural abundance limits commercial use. In this study, a two-step whole-cell bioconversion process was developed for the microbial production of hesperetin from naringenin in Escherichia coli. The 4-hydroxyphenylacetate-3-hydroxylase enzyme complex (HpaBC) enabled cytochrome P450-independent conversion of naringenin to eriodictyol. Subsequent 4′-O-methylation was achieved using a plant-derived flavonoid 4'-O-methyltransferase (FOMT) coupled with a halide methyltransferase (HMT) for in situ S-adenosylmethionine (SAM) regeneration. Enzyme activity was first confirmed individually in vitro and in vivo, followed by integration into recombinant whole-cell systems, co-expressing all desired enzymes. Process optimization through delayed co-substrate addition, improving induction conditions, and machine learning-guided parameter selection increased hesperetin yields up to 70.6% with minimal byproduct formation. This work demonstrates the feasibility of combining process development and digital optimization strategies for the sustainable production of methylated flavonoids in microbial systems. The resulting E. coli platform provides a scalable blueprint for future biotechnological applications involving cofactor-dependent plant secondary metabolism.
KW - halide methyltransferase hesperetin
KW - HpaBC
KW - O-methyltransferase
KW - whole-cell biocatalysis
UR - http://www.scopus.com/inward/record.url?scp=105031062779&partnerID=8YFLogxK
U2 - 10.1002/elsc.70069
DO - 10.1002/elsc.70069
M3 - Article
AN - SCOPUS:105031062779
VL - 26
JO - Engineering in life sciences
JF - Engineering in life sciences
SN - 1618-0240
IS - 2
M1 - e70069
ER -