Efficient heterologous expression of cytochrome P450 enzymes in microorganisms for the biosynthesis of natural products

Hu, Baodong; Zhao, Xinrui; Wang, Endao; Zhou, Jingwen; Li, Jianghua; Chen, Jian; Du, Guocheng

doi:10.1080/07388551.2022.2029344

Cited by 42 publications

(21 citation statements)

References 113 publications

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“…Additional efforts have to be spent to redesign the P450s integration in an E. coli background and/or shift to a more suitable chassis in which better expression can be attained. − Heterologous metabolic circuits in classical hosts such as E. coli, Saccharomyces cerevisiae, or Komagataella phaffii are constantly more complex and intertwined, using system biology knowledge and technical tools gathered in the biofoundries.…”

Section: Discussionmentioning

confidence: 99%

β-Cryptoxanthin Production in Escherichia coli by Optimization of the Cytochrome P450 CYP97H1 Activity

Lautier

Smith

Yang

et al. 2023

J. Agric. Food Chem.

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Cytochromes P450, forming a superfamily of monooxygenases containing heme as a cofactor, show great versatility in substrate specificity. Metabolic engineering can take advantage of this feature to unlock novel metabolic pathways. However, the cytochromes P450 often show difficulty being expressed in a heterologous chassis. As a case study in the prokaryotic host Escherichia coli, the heterologous synthesis of β-cryptoxanthin was addressed. This carotenoid intermediate is difficult to produce, as its synthesis requires a monoterminal hydroxylation of β-carotene whereas most of the classic carotene hydroxylases are dihydroxylases. This study was focused on the optimization of the in vivo activity of CYP97H1, an original P450 β-carotene monohydroxylase. Engineering the N-terminal part of CYP97H1, identifying the matching redox partners, defining the optimal cellular background and adjusting the culture and induction conditions improved the production by 400 times compared to that of the initial strain, representing 2.7 mg/L β-cryptoxanthin and 20% of the total carotenoids produced.

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Section: Discussionmentioning

confidence: 99%

β-Cryptoxanthin Production in Escherichia coli by Optimization of the Cytochrome P450 CYP97H1 Activity

Lautier

Smith

Yang

et al. 2023

J. Agric. Food Chem.

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“…Whole-cell microorganisms not only show the ability to catalyze reaction efficiency, but also exhibit a low consideration for environmental problems. Whole-cell biocatalysts are becoming the most preferred approach for the industrial production of anticancer medicine [ 12 ]. Moreover, microbial production provides eco-friendly and efficient approaches for the development of anticancer drugs [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Microorganisms for Ginsenosides Biosynthesis: Recent Progress, Challenges, and Perspectives

2023

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Ginsenosides are major bioactive compounds present in the Panax species. Ginsenosides exhibit various pharmaceutical properties, including anticancer, anti-inflammatory, antimetastatic, hypertension, and neurodegenerative disorder activities. Although several commercial products have been presented on the market, most of the current chemical processes have an unfriendly environment and a high cost of downstream processing. Compared to plant extraction, microbial production exhibits high efficiency, high selectivity, and saves time for the manufacturing of industrial products. To reach the full potential of the pharmaceutical resource of ginsenoside, a suitable microorganism has been developed as a novel approach. In this review, cell biological mechanisms in anticancer activities and the present state of research on the production of ginsenosides are summarized. Microbial hosts, including native endophytes and engineered microbes, have been used as novel and promising approaches. Furthermore, the present challenges and perspectives of using microbial hosts to produce ginsenosides have been discussed.

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“…Cytochrome P450 enzymes (P450s, CYPs) are heme-containing enzymes that catalyze various types of chemical reactions on a variety of substrates ( Hu et al, 2022b ). Importantly, they are able to catalyze the regioselective and stereoselective oxidations of C-H bonds ( Urlacher and Girhard, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Efficient hydroxylation of flavonoids by using whole-cell P450 sca-2 biocatalyst in Escherichia coli

Zhao²,

Zhou³

et al. 2023

Front. Bioeng. Biotechnol.

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The hydroxylation is an important way to generate the functionalized derivatives of flavonoids. However, the efficient hydroxylation of flavonoids by bacterial P450 enzymes is rarely reported. Here, a bacterial P450 sca-2mut whole-cell biocatalyst with an outstanding 3′-hydroxylation activity for the efficient hydroxylation of a variety of flavonoids was first reported. The whole-cell activity of sca-2mut was enhanced using a novel combination of flavodoxin Fld and flavodoxin reductase Fpr from Escherichia coli. In addition, the double mutant of sca-2mut (R88A/S96A) exhibited an improved hydroxylation performance for flavonoids through the enzymatic engineering. Moreover, the whole-cell activity of sca-2mut (R88A/S96A) was further enhanced by the optimization of whole-cell biocatalytic conditions. Finally, eriodictyol, dihydroquercetin, luteolin, and 7,3′,4′-trihydroxyisoflavone, as examples of flavanone, flavanonol, flavone, and isoflavone, were produced by whole-cell biocatalysis using naringenin, dihydrokaempferol, apigenin, and daidzein as the substrates, with the conversion yield of 77%, 66%, 32%, and 75%, respectively. The strategy used in this study provided an effective method for the further hydroxylation of other high value-added compounds.

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Efficient heterologous expression of cytochrome P450 enzymes in microorganisms for the biosynthesis of natural products

Cited by 42 publications

References 113 publications

β-Cryptoxanthin Production in Escherichia coli by Optimization of the Cytochrome P450 CYP97H1 Activity

β-Cryptoxanthin Production in Escherichia coli by Optimization of the Cytochrome P450 CYP97H1 Activity

Microorganisms for Ginsenosides Biosynthesis: Recent Progress, Challenges, and Perspectives

Efficient hydroxylation of flavonoids by using whole-cell P450 sca-2 biocatalyst in Escherichia coli

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