Recent Advances and Challenges in the Production of Hydroxylated Natural Products Using Microorganisms DOI Creative Commons
Chang Sun,

Rumei Zeng,

Tianpeng Chen

et al.

Fermentation, Journal Year: 2024, Volume and Issue: 10(12), P. 604 - 604

Published: Nov. 26, 2024

Hydroxylation reaction is a significant source of structural diversity in natural products (NPs), playing crucial role improving the bioactivity, solubility, and stability product molecules. This review summarizes latest research progress field hydroxylation, focusing on several key hydroxylases involved biosynthesis NPs, including cytochrome P450 monooxygenases, α-ketoglutarate-dependent hydroxylases, flavin-dependent monooxygenases. These enzymes achieve selective hydroxylation modification various such as terpenoids, flavonoids, steroids, through different catalytic mechanisms. systematically recent advances amino acids, lipids, phenylpropanoids, demonstrating potential synthetic biology strategies constructing artificial biosynthetic pathways producing hydroxylated derivatives. Through metabolic engineering, enzyme genetic combined with intelligence-assisted technologies, series engineered strains have been successfully constructed for efficient production NPs their derivatives, achieving synthesis NPs. has provided new avenues drug development, functional food, biomaterial also offered ideas industrial these compounds. In future, integrating pathway design, directed evolution, dynamic regulation, intelligence technology expected to further expand application enzyme-catalyzed reactions green complex promoting heights.

Language: Английский

Optimizing the Biosynthesis of Dihydroquercetin from Naringenin in Saccharomyces cerevisiae DOI

Yuyang Pan,

Zhibo Yan,

Songlyu Xue

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(9), P. 4880 - 4887

Published: Feb. 22, 2024

Dihydroquercetin (DHQ), known for its varied physiological benefits, is widely used in the food, chemical, and pharmaceutical industries. However, efficiency of DHQ synthesis significantly limited by substantial accumulation intermediates during biosynthesis. In this study, production was achieved integrating genes from various organisms into yeast chromosome expression flavanone-3-hydroxylase (F3H), flavonoid-3′-hydroxylase, cytochrome P450 reductase. A computer-aided protein design approach led to development optimal F3H mutant P221A, resulting a 1.67-fold increase yield naringenin (NAR) compared with control. Subsequently, analysis enzyme reaction optimization culture medium composition, 637.29 ± 20.35 mg/L synthesized 800 NAR. This corresponds remarkable conversion rate 71.26%, one highest reported values NAR date.

Language: Английский

Citations

6
Recent advancements in flavonoid production through engineering microbial systems DOI
Yunhee Hwang, Myung Hyun Noh, Gyoo Yeol Jung

et al.

Biotechnology and Bioprocess Engineering, Journal Year: 2024, Volume and Issue: 29(5), P. 792 - 805

Published: June 27, 2024

Language: Английский

Citations

4
Efficient Biosynthesis of Furanocoumarin Intermediate Marmesin by Engineered Escherichia coli DOI

Baodong Hu,

Jingwen Zhou, Jianghua Li

et al.

ACS Synthetic Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Marmesin, a plant dihydrofuranocoumarin, is an important intermediate in the synthesis of linear furanocoumarins and exhibits variety pharmacological activities. However, due to lack efficient prenyltransferases, incompatibility redox partners for P450 enzymes, insufficient supply precursor (DMAPP), microbial marmesin remained at extremely low level. Here, we report biosynthesis Escherichia coli by screening robust 6-prenyltransferase PpPT1 synthase PpDCΔ2–29 from Peucedanum praeruptorum. Next, activities were enhanced using fusion protein tags partner engineering, respectively. In addition, was further improved strengthening methylerythritol phosphate (MEP) pathway increase availability DMAPP optimizing modular engineered strain. Finally, titer reached 203.69 mg L–1 fed-batch fermentation with molar conversion rate umbelliferone 81.4%, which highest production microorganisms. The applied strategy marmesin-producing strain constructed this study lay foundation green valuable complex furanocoumarins.

Language: Английский

Citations

0
Efficient stereoselective hydroxylation of deoxycholic acid by the robust whole-cell cytochrome P450 CYP107D1 biocatalyst DOI Creative Commons
Chixiang Sun,

Baodong Hu,

Yanchun Li

et al.

Synthetic and Systems Biotechnology, Journal Year: 2023, Volume and Issue: 8(4), P. 741 - 748

Published: Nov. 26, 2023

Deoxycholic acid (DCA) has been authorized by the Federal Drug Agency for cosmetic reduction of redundant submental fat. The hydroxylated product (6β-OH DCA) was developed to improve solubility and pharmaceutic properties DCA further applications. Herein, a combinatorial catalytic strategy applied construct powerful Cytochrome P450 biocatalyst (CYP107D1, OleP) convert 6β-OH DCA. Firstly, weak expression OleP significantly improved using pRSFDuet-1 plasmid in E. coli C41 (DE3) strain. Next, supply heme enhanced moderate overexpression crucial genes biosynthetic pathway. In addition, new biosensor select appropriate redox partner. Furthermore, cost-effective whole-cell system constructed, resulting highest reported conversion rate (from 4.8% 99.1%). strategies this study provide an efficient method synthesize high-value-added compounds P450s.

Language: Английский

Citations

7
Rational Design of Key Enzymes to Efficiently Synthesize Phycocyanobilin in Escherichia coli DOI Creative Commons
Ziwei Wang, Jingwen Zhou, Jianghua Li

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 301 - 301

Published: March 3, 2024

Phycocyanobilin (PCB) is a natural blue tetrapyrrole chromophore that found in phycocyanin and plays an essential role photosynthesis. Due to PCB’s antioxidation, anti-inflammatory anti-cancer properties, it has been utilized the food, pharmaceutical cosmetic industries. Currently, extraction of PCB from Spirulina involves complex processes, which led increasing interest biosynthesis Escherichia coli. However, titer remains low because poor activity key enzymes insufficient precursor supply. Here, synthesis was firstly improved by screening optimal heme oxygenase (HO) Thermosynechococcus elongatus BP-1(HOT) PCB: ferredoxin oxidoreductase Synechocystis sp. PCC6803 (PcyAS). In addition, based on rational design infrared fluorescence method for high-throughput screening, mutants HOT(F29W/K166D) PcyAS(D220G/H74M) with significantly higher activities were obtained. Furthermore, DNA scaffold applied assembly HOT PcyAS reduce spatial barriers, supply enhanced via moderate overexpression hemB hemH, resulting highest (184.20 mg/L) obtained 5 L fermenter. The strategies this study lay foundation industrial production its derivatives.

Language: Английский

Citations

2
Recent Advances and Challenges in the Production of Hydroxylated Natural Products Using Microorganisms DOI Creative Commons
Chang Sun,

Rumei Zeng,

Tianpeng Chen

et al.

Fermentation, Journal Year: 2024, Volume and Issue: 10(12), P. 604 - 604

Published: Nov. 26, 2024

Hydroxylation reaction is a significant source of structural diversity in natural products (NPs), playing crucial role improving the bioactivity, solubility, and stability product molecules. This review summarizes latest research progress field hydroxylation, focusing on several key hydroxylases involved biosynthesis NPs, including cytochrome P450 monooxygenases, α-ketoglutarate-dependent hydroxylases, flavin-dependent monooxygenases. These enzymes achieve selective hydroxylation modification various such as terpenoids, flavonoids, steroids, through different catalytic mechanisms. systematically recent advances amino acids, lipids, phenylpropanoids, demonstrating potential synthetic biology strategies constructing artificial biosynthetic pathways producing hydroxylated derivatives. Through metabolic engineering, enzyme genetic combined with intelligence-assisted technologies, series engineered strains have been successfully constructed for efficient production NPs their derivatives, achieving synthesis NPs. has provided new avenues drug development, functional food, biomaterial also offered ideas industrial these compounds. In future, integrating pathway design, directed evolution, dynamic regulation, intelligence technology expected to further expand application enzyme-catalyzed reactions green complex promoting heights.

Language: Английский

Citations

1