Biosynthesis with Fluorine

Klopries, Stephan; Koopmans, Kyra R.M.; Sánchez-García, Elsa; Schulz, Frank

doi:10.1002/cbic.201300750

Cited by 4 publications

(4 citation statements)

References 19 publications

(41 reference statements)

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“…Hence, the preparation of fluorinated polyketide has been investigated using PKS from fluoroacetate (Fig. 6 ) (Hong et al 2008 ; Klopries et al 2014 ; Walker et al 2013 ; Wu et al 2020a ). Similarly, fluorinated polyketones can also be obtained from fluoromalonate and fluorobutyrate, which are derived from the basic building blocks malonate and butyric acid, respectively (Klopries et al 2014 ; Thuronyi and Chang 2015 ; Thuronyi et al 2017 ).…”

Section: Enzymatic Synthesis Of Fluorinated Compoundsmentioning

confidence: 99%

Enzymatic synthesis of fluorinated compounds

Cheng

2021

Appl Microbiol Biotechnol

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Fluorinated compounds are widely used in the fields of molecular imaging, pharmaceuticals, and materials. Fluorinated natural products in nature are rare, and the introduction of fluorine atoms into organic compound molecules can give these compounds new functions and make them have better performance. Therefore, the synthesis of fluorides has attracted more and more attention from biologists and chemists. Even so, achieving selective fluorination is still a huge challenge under mild conditions. In this review, the research progress of enzymatic synthesis of fluorinated compounds is summarized since 2015, including cytochrome P450 enzymes, aldolases, fluoroacetyl coenzyme A thioesterases, lipases, transaminases, reductive aminases, purine nucleoside phosphorylases, polyketide synthases, fluoroacetate dehalogenases, tyrosine phenol-lyases, glycosidases, fluorinases, and multienzyme system. Of all enzyme-catalyzed synthesis methods, the direct formation of the C-F bond by fluorinase is the most effective and promising method. The structure and catalytic mechanism of fluorinase are introduced to understand fluorobiochemistry. Furthermore, the distribution, applications, and future development trends of fluorinated compounds are also outlined. Hopefully, this review will help researchers to understand the significance of enzymatic methods for the synthesis of fluorinated compounds and find or create excellent fluoride synthase in future research. Key points • Fluorinated compounds are distributed in plants and microorganisms, and are used in imaging, medicine, materials science . • Enzyme catalysis is essential for the synthesis of fluorinated compounds . • The loop structure of fluorinase is the key to forming the C-F bond . Supplementary Information The online version contains supplementary material available at 10.1007/s00253-021-11608-0.

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Section: Enzymatic Synthesis Of Fluorinated Compoundsmentioning

confidence: 99%

Enzymatic synthesis of fluorinated compounds

Cheng

2021

Appl Microbiol Biotechnol

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“…Due to the high electronegativity and small size of fluorine, introducing fluorine into organic compounds can significantly affect their hydrophobicity and physiological properties. − Thus, organofluorine compounds play important roles in the field of agrochemicals. − In recent years, there has been an increase in the number of fluorine-containing pesticides (such as fluridone and fenpyrazone) approved for commercial use. Although methods for introducing fluorine have been well developed in organic synthesis, the widespread use of hazardous fluorinating agents − has made greener and more sustainable means of fluorination highly desirable. − Therefore, developing biosynthetic methods for organofluorine compounds is a promising approach.…”

Section: Introductionmentioning

confidence: 99%

Enzyme Engineering Renders Chlorinase the Activity of Fluorinase

Jiang,

Yao,

Niu

et al. 2024

J. Agric. Food Chem.

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Organofluorine compounds have attracted substantial attention owing to their wide application in agrochemistry. Fluorinase (FlA) is a unique enzyme in nature that can incorporate fluorine into an organic molecule. Chlorinase (SalL) has a similar mechanism as fluorinase and can use chloride but not fluoride as a substrate to generate 5′-chloro-deoxyadenosine (5′-ClDA) from S-adenosyl-L-methionine (SAM). Therefore, identifying the features that lead to this selectivity for halide ions is highly important. Here, we engineered SalL to gain the function of FlA. We found that residue Tyr70 plays a key role in this conversion through alanine scanning. Site-saturation mutagenesis experiments demonstrated that Y70A/C/S/T/G all exhibited obvious fluorinase activity. The G131S mutant of SalL, in which the previously thought crucial residue Ser158 for fluoride binding in FlA was introduced, did not exhibit fluorination activity. Compared with the Y70T single mutant, the double mutant Y70T/W129F increased 5′-fluoro-5-deoxyadenosine (5′-FDA) production by 76%. The quantum mechanics (QM)/molecular mechanics (MM) calculations suggested that the lower energy barriers and shorter nucleophilic distance from F − to SAM in the mutants than in the SalL wild-type may contribute to the activity. Therefore, our study not only renders SalL the activity of FlA but also sheds light on the enzyme selectivity between fluoride versus chloride.

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“…Organic fluorides are important compounds that are widely used in the fields of pharmaceuticals, molecular imaging, and materials ( Klopries et al, 2014 ; Wu et al, 2020a ; Cheng and Ma, 2021 ). Fluorinated natural products are extremely rare in nature ( Cheng and Ma, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Fluorinated natural products are extremely rare in nature ( Cheng and Ma, 2021 ). However, the introduction of fluorine atoms into organic compound molecules can often give these compounds new functions and make them have better performance ( Klopries et al, 2014 ; Ningning et al, 2020 ; Tu et al, 2020 ). The target compounds doped with fluorine are endowed with stronger stability and activity ( Tu et al, 2020 ), longer half-life, and better bioabsorbability ( Ningning et al, 2020 ), especially in the fields of pharmaceutical intermediates, cancer treatment ( Lowe et al, 2019 ), antiviral agents, photovoltaics, diagnostic probes ( Onega et al, 2010 ) and bioinspired materials ( Ningning et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic synthesis of 2-fluoro-3-hydroxypropionic acid

Liu

Yuan²,

Jin³

et al. 2022

Front. Bioeng. Biotechnol.

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Fluorine has become an important element for the design of synthetic molecules for use in medicine, agriculture, and materials. The introduction of fluorine atoms into organic compound molecules can often give these compounds new functions and make them have better performance. Despite the many advantages provided by fluorine for tuning key molecular properties, it is rarely found in natural metabolism. We seek to expand the molecular space available for discovery through the development of new biosynthetic strategies that cross synthetic with natural compounds. Towards this goal, 2-fluoro-3-hydroxypropionic acid (2-F-3-HP) was first synthesized using E. coli coexpressing methylmalonyl CoA synthase (MatBrp), methylmalonyl CoA reductase (MCR) and malonate transmembrane protein (MadLM). The concentration of 2-F-3-HP reached 50.0 mg/L by whole-cell transformation after 24 h. 2-F-3-HP can be used as the substrate to synthesize other fluorides, such as poly (2-fluoro-3-hydroxypropionic acid) (FP3HP). Being entirely biocatalytic, our procedure provides considerable advantages in terms of environmental and safety impacts over reported chemical methods.

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Biosynthesis with Fluorine

Cited by 4 publications

References 19 publications

Enzymatic synthesis of fluorinated compounds

Enzymatic synthesis of fluorinated compounds

Enzyme Engineering Renders Chlorinase the Activity of Fluorinase

Biocatalytic synthesis of 2-fluoro-3-hydroxypropionic acid

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