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氟化天然产物生物合成的研究进展
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国家自然科学基金（21672161）；天津市科学技术委员会项目（18PTSYJC00140）；天津市教委科研计划项目（2019KJ239）


Advances in biosynthesis of fluorinated products
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    摘要:

    氟元素是一种具有特殊性质的卤素，含氟有机物可广泛应用于生物有机化学、药物化学和生物材料科学等领域。尽管C-F键的合成方法有所创新，但将氟元素掺入到结构复杂的生物活性分子中的方法较少，因此选择性的氟化仍极具挑战性。本文从自然界中氟化天然产物及氟化酶的发现、氟化天然产物的合成通路、氟化天然产物合成机制的意义、氟化酶的进化及氟化物的合成、氟化酶和氟化物的应用等方面进行综述，希望可以为氟化物的生物法合成领域提供信息参考，推进氟化物生物法合成的工业化进程。

    Abstract:

    Fluorine is a kind of halogen with special properties. Fluorine-containing organic substances can be widely used in bioorganic chemistry, medicinal chemistry, biomaterial science and other fields. Despite innovation of synthetic C-F bond forming methods, selective fluorination is still very challenging. Therefore, it is necessary to use fluorine biochemical methods to selectively introduce fluorine into molecules with diverse structures, but few methods can incorporate fluorine into bioactive molecules with complex structures. Therefore, we review here the discovery of fluorinated natural products and fluorinases in nature, the synthetic pathway of fluorinated natural products, the significance of fluorinated natural product synthesis mechanism, the evolution of fluorinases and the synthesis of fluoride, and the application of fluorinases and fluoride. This review will provide information for fluoride biosynthesis and promote the industrialization process of fluoride biosynthesis.

    参考文献
    [1] Dickson AG, Goyet C. Handbook of Methods for the Analysis of the Various Parameters of the Carbon Dioxide System in Sea Water. Version 2. Washington, DC:Oak Ridge National Lab, 1994.
    [2] Kirk KL. Fluorination in medicinal chemistry:methods, strategies, and recent developments. Organic Process Research & Development, 2008, 12(2):305-321.
    [3] Isanbor C, O'Hagan D. Fluorine in medicinal chemistry:a review of anti-cancer agents. Journal of Fluorine Chemistry, 2006, 127(3):303-319.
    [4] O'Hagan D. Fluorine in health care:organofluorine containing blockbuster drugs. Journal of Fluorine Chemistry, 2010, 131(11):1071-1081.
    [5] Hagmann WK. The many roles for fluorine in medicinal chemistry. Journal of Medicinal Chemistry, 2008, 51(15):4359-4369.
    [6] Wu LR, Maglangit F, Deng H. Fluorine biocatalysis. Current Opinion in Chemical Biology, 2020, 55:119-126.
    [7] Deng H, O'Hagan D. The fluorinase, the chlorinase and the duf-62 enzymes. Current Opinion in Chemical Biology, 2008, 12(5):582-592.
    [8] Henkel T, Brunne RM, Müller H, Reichel F. Statistical investigation into the structural complementarity of natural products and synthetic compounds. Angewandte Chemie International Edition, 1999, 38(5):643-647.
    [9] Gribble GW. Occurrence of halogenated alkaloids. The Alkaloids:Chemistry and Biology, 2012, 71:1-165.
    [10] Carvalho MF, Oliveira RS. Natural production of fluorinated compounds and biotechnological prospects of the fluorinase enzyme. Critical Reviews in Biotechnology, 2017, 37(7):880-897.
    [11] Deng H, O'Hagan D, Schaffrath C. Fluorometabolite biosynthesis and the fluorinase from Streptomyces cattleya. Natural Product Reports, 2004, 21(6):773.
    [12] Harper DB, O'Hagan D. The fluorinated natural products. Natural Product Reports, 1994, 11:123-133.
    [13] Marais JSC, Du TPJ. The isolation of the toxic principle "potassium cymonate" from "Gifblaar" Dichapetalum cymosum (Hook) Engl. Onderstepoort Journal Veterinary Science and Animal Industry, 1943, 18:203-206.
    [14] Ma L, Bartholome A, Tong MH, Qin ZW, Yu Y, Shepherd T, Kyeremeh K, Deng H, O'Hagan D. Identification of a fluorometabolite from Streptomyces sp. MA37:(2R3S4S)-5-fluoro-2,3,4-trihydroxypentanoic acid. Chemical Science, 2015, 6(2):1414-1419.
    [15] Ni CF, Hu JB. The unique fluorine effects in organic reactions:recent facts and insights into fluoroalkylations. Chemical Society Reviews, 2016, 45(20):5441-5454.
    [16] Reichel M, Karaghiosoff K. Reagents for selective fluoromethylation:a challenge in organofluorine chemistry. Angewandte Chemie International Edition, 2020, 59(30):12268-12281.
    [17] Truppo MD. Biocatalysis in the pharmaceutical industry:the need for speed. ACS Medicinal Chemistry Letters, 2017, 8(5):476-480.
    [18] Fryszkowska A, Devine PN. Biocatalysis in drug discovery and development. Current Opinion in Chemical Biology, 2020, 55:151-160.
    [19] Dong CJ, Huang FL, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH. Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature, 2004, 427(6974):561-565.
    [20] O'Hagan D, Schaffrath C, Cobb SL, Hamilton JTG, Murphy CD. Biosynthesis of an organofluorine molecule. Nature, 2002, 416(6878):279.
    [21] Ma L, Li YF, Meng LP, Deng H, Li YY, Zhang Q, Diao AP. Biological fluorination from the sea:discovery of a SAM-dependent nucleophilic fluorinating enzyme from the marine-derived bacterium Streptomyces xinghaiensis NRRL B24674. RSC Advances, 2016, 6(32):27047-27051.
    [22] Deng H, Ma L, Bandaranayaka N, Qin ZW, Mann G, Kyeremeh K, Yu Y, Shepherd T, Naismith JH, O'Hagan D. Identification of Fluorinases from Streptomyces sp. MA37, Norcardia brasiliensis, and Actinoplanes sp. N902-109 by genome mining. ChemBioChem, 2014, 15(3):364-368.
    [23] Huang S, Ma L, Tong MH, Yu Y, O'Hagan D, Deng H. Fluoroacetate biosynthesis from the marine-derived bacterium Streptomyces xinghaiensis NRRL B-24674. Organic & Biomolecular Chemistry, 2014, 12(27):4828-4831.
    [24] Sooklal SA, De Koning C, Brady D, Rumbold K. Identification and characterisation of a fluorinase from Actinopolyspora mzabensis. Protein Expression and Purification, 2020, 166:105508.
    [25] Murphy CD, O'Hagan D, Schaffrath C. Identification of a PLP-dependent threonine transaldolase:a novel enzyme involved in 4-fluorothreonine biosynthesis in Streptomyces cattleya. Angewandte Chemie International Edition, 2001, 40(23):4479-4481.
    [26] Huang FL, Haydock SF, Spiteller D, Mironenko T, Li TL, O'Hagan D, Leadlay PF, Spencer JB. The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya:a thioesterase confers resistance to fluoroacetyl-coenzyme A. Chemistry & Biology, 2006, 13(5):475-484.
    [27] O'Hagan D, Deng H. Enzymatic fluorination and biotechnological developments of the fluorinase. Chemical Reviews, 2015, 115(2):634-649.
    [28] Deng H, Cross SM, McGlinchey RP, Hamilton JTG, O'Hagan D. In vitro reconstituted biotransformation of 4-fluorothreonine from fluoride ion:application of the fluorinase. Chemistry & Biology, 2008, 15(12):1268-1276.
    [29] Bartholomé A, Janso JE, Reilly U, O'Hagan D. Fluorometabolite biosynthesis:isotopically labelled glycerol incorporations into the antibiotic nucleocidin in Streptomyces calvus. Organic & Biomolecular Chemistry, 2017, 15(1):61-64.
    [30] Zhu XM, Hackl S, Thaker MN, Kalan L, Weber C, Urgast DS, Krupp EM, Brewer A, Vanner S, Szawiola A, Yim G, Feldmann J, Bechthold A, Wright GD, Zechel DL. Biosynthesis of the fluorinated natural product nucleocidin in Streptomyces calvus is dependent on the bldA-Specified Leu-tRNAUUA molecule. ChemBioChem, 2015, 16(17):2498-2506.
    [31] Feng X, Bello D, Lowe PT, Clark J, O'Hagan D. Two 3ʹ-O-β-glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus. Chemical Science, 2019, 10(41):9501-9505.
    [32] Feng X, Maharik NA, Bartholomé A, Janso JE, Reilly U, O'Hagan D. Incorporation of[2H1]-(1R,2R)-and[2H1]-(1S,2R)-glycerols into the antibiotic nucleocidin in Streptomyces calvus. Organic & Biomolecular Chemistry, 2017, 15(38):8006-8008.
    [33] Zhang SY, Klementz D, Zhu J, Makitrynskyy R, Pasternak ARO, Günther S, Zechel DL, Bechthold A. Genome mining reveals the origin of a bald phenotype and a cryptic nucleocidin gene cluster in Streptomyces asterosporus DSM 41452. Journal of Biotechnology, 2019, 292:23-31.
    [34] O'Hagan D, Harper DB. Fluorine-containing natural products. Journal of Fluorine Chemistry, 1999, 100(1/2):127-133.
    [35] Walker MC, Thuronyi BW, Charkoudian LK, Lowry B, Khosla C, Chang MCY. Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways. Science, 2013, 341(6150):1089-1094.
    [36] Eustáquio AS, O'Hagan D, Moore BS. Engineering fluorometabolite production:fluorinase expression in Salinispora tropica yields fluorosalinosporamide. Journal of Natural Products, 2010, 73(3):378-382.
    [37] Mo SJ, Kim DH, Lee JH, Park JW, Basnet DB, Ban YH, Yoo YJ, Chen SW, Park SR, Choi EA, Kim E, Jin YY, Lee SK, Park JY, Liu Y, Lee MO, Lee KS, Kim SJ, Kim D, Park BC, Lee SG, Kwon HJ, Suh JW, Moore BS, Lim SK, Yoon YJ. Biosynthesis of the Allylmalonyl-CoA extender unit for the FK506 Polyketide synthase proceeds through a dedicated polyketide synthase and facilitates the mutasynthesis of analogues. Journal of the American Chemical Society, 2011, 133(4):976-985.
    [38] Demain AL, Sanchez S. Microbial drug discovery:80 years of progress. The Journal of Antibiotics, 2009, 62(1):5-16.
    [39] Harvey AL, Edrada-Ebel RA, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nature Reviews Drug Discovery, 2015, 14(2):111-129.
    [40] Anderson AS, Wellington EM. The taxonomy of Streptomyces and related genera. International Journal of Systematic and Evolutionary Microbiology, 2001, 51(3):797-814.
    [41] Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural Products, 2012, 75(3):311-335.
    [42] Tang XM, Xu J. Advance in research on the halogenase from microorganism. Chinese Journal of Antibiotics, 2008, 33(11):641-644, 677. (in Chinese) 唐晓敏, 徐俊. 微生物卤代酶研究进展. 中国抗生素杂志, 2008, 33(11):641-644, 677.
    [43] Gao P, Xi LJ, Piao YH, Ruan JS, Huang Y. Analysis of the halogenase gene in actinomycetes from different habitats and its implications for halometabolite discovery. Acta Microbiologica Sinica, 2009, 49(10):1367-1373. (in Chinese) 高鹏, 郗丽君, 朴玉华, 阮继生, 黄英. 不同生境放线菌的卤化酶基因分析及其对卤代产物筛选的意义. 微生物学报, 2009, 49(10):1367-1373.
    [44] Li H, Zhu L, Chen DJ. Recent developments of FADH2- dependent halogenases involved in the biosynthesis of antibiotics. Chinese Journal of Antibiotics, 2010, 35(1):1-6. (in Chinese) 李航, 朱丽, 陈代杰. 参与抗生素生物合成的FADH2依赖型卤化酶研究进展. 中国抗生素杂志, 2010, 35(1):1-6.
    [45] Tong W, Huang Q, Li M, Wang JB. Enzyme-catalyzed C-F bond formation and cleavage. Bioresources and Bioprocessing, 2019, 6(1):46, doi:10.1186/s40643-019-0280-6.
    [46] Sun HH, Yeo WL, Lim YH, Chew X, Smith DJ, Xue B, Chan KP, Robinson RC, Robins EG, Zhao HM, Ang EL. Directed evolution of a fluorinase for improved fluorination efficiency with a non-native substrate. Angewandte Chemie, 2016, 128(46):14489-14492.
    [47] Sun H, Zhao H, Ang EL. A coupled chlorinase-fluorinase system with a high efficiency of trans-halogenation and a shared substrate tolerance. Chemical Communications, 2018, 54(68):9458-9461.
    [48] Lowe PT, Cobb SL, O'Hagan D. An enzymatic Finkelstein reaction:fluorinase catalyses direct halogen exchange. Organic & Biomolecular Chemistry, 2019, 17(32):7493-7496.
    [49] Thompson S, Onega M, Ashworth S, Fleming IN, Passchier J, O'Hagan D. A two-step fluorinase enzyme mediated 18F labelling of an RGD peptide for positron emission tomography. Chemical Communications, 2015, 51(70):13542-13545.
    [50] Lowe PT, Dall'Angelo S, Devine A, Zanda M, O'Hagan D. Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging. ChemBioChem, 2018, 19(18):1969-1978.
    [51] Lowe PT, Dall'Angelo S, Fleming IN, Piras M, Zanda M, O'Hagan D. Enzymatic radiosynthesis of a 18F-Glu-Ureido-Lys ligand for the prostate-specific membrane antigen (PSMA). Organic & Biomolecular Chemistry, 2019, 17(6):1480-1486.
    [52] Wu LR, Tong MH, Raab A, Fang Q, Wang S, Kyeremeh K, Yu Y, Deng H. An unusual metal-bound 4-fluorothreonine transaldolase from Streptomyces sp. MA37 catalyses promiscuous transaldol reactions. Applied Microbiology and Biotechnology, 2020, 104(9):3885-3896.
    [53] Zhang HX, Tian SX, Yue Y, Li M, Tong W, Xu GY, Chen B, Ma M, Li YW, Wang JB. Semirational design of fluoroacetate dehalogenase RPA1163 for kinetic resolution of α-Fluorocarboxylic acids on a gram scale. ACS Catalysis, 2020, 10(5):3143-3151.
    [54] Saadi J, Wennemers H. Enantioselective aldol reactions with masked fluoroacetates. Nature Chemistry, 2016, 8(3):276-280.
    [55] Fang J, Hait D, Head-Gordon M, Chang MCY. Chemoenzymatic platform for synthesis of chiral organofluorines based on type II aldolases. Angewandte Chemie International Edition, 2019, 58(34):11841-11845.
    [56] Tu CH, Zhou J, Peng L, Man SL, Ma L. Self-assembled nano-aggregates of fluorinases demonstrate enhanced enzymatic activity, thermostability and reusability. Biomaterials Science, 2020, 8(2):648-656.
    [57] Li NN, Hu BJ, Wang AM, Li HM, Yin YC, Mao TY, Xie T. Facile bioinspired preparation of Fluorinase@Fluoridated hydroxyapatite nanoflowers for the biosynthesis of 5'-fluorodeoxy adenosine. Sustainability, 2020, 12(1):431.
    [58] Markakis K, Lowe PT, Davison-Gates L, O'Hagan D, Rosser SJ, Elfick A. An engineered E. coli strain for direct in vivo fluorination. ChemBioChem, 2020, 21(13):1856-1860.
    [59] Yamaga LYI, Thom AF, Wagner J, Baroni RH, Hidal JT, Funari MG. The effect of catecholamines on the glucose uptake in brown adipose tissue demonstrated by 18F-FDG PET/CT in a patient with adrenal pheochromocytoma. European Journal of Nuclear Medicine and Molecular Imaging, 2008, 35(2):446-447.
    [60] Sharma R, Aboagye E. Development of radiotracers for oncology-the interface with pharmacology. British Journal of Pharmacology, 2011, 163(8):1565-1585.
    [61] Soussan M, Hyafil F. Can FDG-PET imaging play a role in guiding indications to endovascular treatments in patients presenting acute aortic syndromes? Journal of Nuclear Cardiology, 2019, 26(2):642-644.
    [62] Cai LS, Lu SY, Pike VW. Chemistry with[18F]fluoride ion. European Journal of Organic Chemistry, 2008, 2008(17):2853-2873.
    [63] Clark J, O'Hagan D. Strategies for radiolabelling antibody, antibody fragments and affibodies with fluorine-18 as tracers for positron emission tomography (PET). Journal of Fluorine Chemistry, 2017, 203:31-46.
    [64] Thompson S, Zhang QZ, Onega M, McMahon S, Fleming I, Ashworth S, Naismith JH, Passchier J, O'Hagan D. A localized tolerance in the substrate specificity of the fluorinase enzyme enables "Last-Step" 18F fluorination of a RGD peptide under ambient aqueous conditions. Angewandte Chemie International Edition, 2014, 53(34):8913-8918.
    [65] Li XG, Domarkas J, O'Hagan D. Fluorinase mediated chemoenzymatic synthesis of[18F]-fluoroacetate. Chemical Communications, 2010, 46(41):7819-7821.
    [66] Dall'Angelo S, Bandaranayaka N, Windhorst AD, Vugts DJ, van der Born D, Onega M, Schweiger LF, Zanda M, O'Hagan D. Tumour imaging by Positron Emission Tomography using fluorinase generated 5-[18F] fluoro-5-deoxyribose as a novel tracer. Nuclear Medicine and Biology, 2013, 40(4):464-470.
    [67] Winkler M, Domarkas J, Schweiger LF, O'Hagan D. Fluorinase-coupled base swaps:synthesis of[18F]-5'-Deoxy-5'-fluorouridines. Angewandte Chemie International Edition, 2008, 47(52):10141-10143.
    [68] Li XG, Autio A, Ahtinen H, Helariutta K, Liljenbäck H, Jalkanen S, Roivainen A, Airaksinen AJ. Translating the concept of peptidelabeling with 5-deoxy-5-[18F]fluororibose into preclinical practice:18F-labeling of Siglec-9 peptide for PET imaging of inflammation. Chemical Communications, 2013, 49(35):3682-3684.
    [69] Dall'Angelo S, Zhang QZ, Fleming IN, Piras M, Schweiger LF, O'Hagan D, Zanda M. Efficient bioconjugation of 5-fluoro-5-deoxy-ribose (FDR) to RGD peptides for positron emission tomography (PET) imaging of αvβ3 integrin receptor. Organic & Biomolecular Chemistry, 2013, 11(27):4551-4558.
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任思羽,程新宽,张宇辉,庄建文,马龙. 氟化天然产物生物合成的研究进展[J]. 微生物学报, 2021, 61(3): 524-538

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