Nitric oxide as a source for bacterial triazole biosynthesis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
18
11
2019
accepted:
02
03
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
25
7
2020
Statut:
epublish
Résumé
The heterocycle 1,2,3-triazole is among the most versatile chemical scaffolds and has been widely used in diverse fields. However, how nature creates this nitrogen-rich ring system remains unknown. Here, we report the biosynthetic route to the triazole-bearing antimetabolite 8-azaguanine. We reveal that its triazole moiety can be assembled through an enzymatic and non-enzymatic cascade, in which nitric oxide is used as a building block. These results expand our knowledge of the physiological role of nitric oxide synthase in building natural products with a nitrogen-nitrogen bond, and should also inspire the development of synthetic biology approaches for triazole production.
Identifiants
pubmed: 32235841
doi: 10.1038/s41467-020-15420-8
pii: 10.1038/s41467-020-15420-8
pmc: PMC7109123
doi:
Substances chimiques
Bacterial Proteins
0
Biological Products
0
Triazoles
0
Nitric Oxide
31C4KY9ESH
Nitric Oxide Synthase
EC 1.14.13.39
Nitrogen
N762921K75
Azaguanine
Q150359I72
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1614Références
Dheer, D., Singh, V. & Shankar, R. Medicinal attributes of 1,2,3-triazoles: current developments. Bioorg. Chem. 71, 30–54 (2017).
doi: 10.1016/j.bioorg.2017.01.010
pubmed: 28126288
pmcid: 28126288
Schulze, B. & Schubert, U. S. Beyond click chemistry—supramolecular interactions of 1,2,3-triazoles. Chem. Soc. Rev. 43, 2522–2571 (2014).
doi: 10.1039/c3cs60386e
pubmed: 24492745
pmcid: 24492745
Juríček, M., Kouwer, P. H. J. & Rowan, A. E. Triazole: a unique building block for the construction of functional materials. Chem. Commun. 47, 8740–8749 (2011).
doi: 10.1039/c1cc10685f
Pedersen, D. S. & Abell, A. 1,2,3-Triazoles in peptidomimetic chemistry. Eur. J. Org. Chem. 2011, 2399–2411 (2011).
doi: 10.1002/ejoc.201100157
Kaur, K. & Kumar, V. Triazole and oxadiazole containing natural products: a review. Nat. Products J. 4, 115–130 (2014).
doi: 10.2174/221031550402141009100114
Anzai, K., Nagatsu, J. & Suzuki, S. Pathocidin, a new antifungal antibiotic, I. Isolation, physical and chemical properties, and biological activities. J. Antibiot. 14, 340–342 (1961).
pubmed: 14036815
pmcid: 14036815
Grunberger, D. & Grunberger, G. in Mechanism of Action of Antieukaryotic and Antiviral Compounds (ed. Hahn, F. E.) 110–123 (1979).
Nelson, J. A., Carpenter, J. W., Rose, L. M. & Adamson, D. J. Mechanisms of action of 6-thioguanine, 6-mercaptopurine, and 8-azaguanine. Cancer Res. 35, 2872–2878 (1975).
pubmed: 1157053
pmcid: 1157053
Du, Y.-L., He, H.-Y., Higgins, M. A. & Ryan, K. S. A heme-dependent enzyme forms the nitrogen–nitrogen bond in piperazate. Nat. Chem. Biol. 13, 836–838 (2017).
doi: 10.1038/nchembio.2411
pubmed: 28628093
pmcid: 28628093
Sugai, Y., Katsuyama, Y. & Ohnishi, Y. A nitrous acid biosynthetic pathway for diazo group formation in bacteria. Nat. Chem. Biol. 12, 73–75 (2016).
doi: 10.1038/nchembio.1991
pubmed: 26689788
pmcid: 26689788
Waldman, A. J. & Balskus, E. P. Discovery of a diazo-forming enzyme in cremeomycin biosynthesis. J. Org. Chem. 83, 7539–7546 (2018).
doi: 10.1021/acs.joc.8b00367
pubmed: 29771512
pmcid: 29771512
Ng, T. L., Rohac, R., Mitchell, A. J., Boal, A. K. & Balskus, E. P. An N-nitrosating metalloenzyme constructs the pharmacophore of streptozotocin. Nature 566, 94 (2019).
doi: 10.1038/s41586-019-0894-z
pubmed: 30728519
pmcid: 30728519
He, H.-Y., Henderson, A. C., Du, Y.-L. & Ryan, K. S. Two-enzyme pathway links L-arginine to nitric oxide in N-Nitroso biosynthesis. J. Am. Chem. Soc. 141, 4026–4033 (2019).
doi: 10.1021/jacs.8b13049
pubmed: 30763082
pmcid: 30763082
Matsuda, K. et al. Discovery of unprecedented hydrazine-forming machinery in bacteria. J. Am. Chem. Soc. 140, 9083–9086 (2018).
doi: 10.1021/jacs.8b05354
pubmed: 30001119
pmcid: 30001119
Wang, K.-K. A. et al. Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin. Nat. Commun. 9, 3687 (2018).
doi: 10.1038/s41467-018-06083-7
pubmed: 30206228
pmcid: 30206228
Zhao, G. et al. The biosynthetic gene cluster of pyrazomycin-a C-nucleoside antibiotic with a rare pyrazole moiety. ChemBioChem https://doi.org/10.1002/cbic.201900449 (2019).
doi: 10.1002/cbic.201900449
pubmed: 31814269
pmcid: 31814269
Wang, S.-A. et al. Identification of the formycin a biosynthetic gene cluster from Streptomyces kaniharaensis illustrates the interplay between biological pyrazolopyrimidine formation and de Novo purine biosynthesis. J. Am. Chem. Soc. 141, 6127–6131 (2019).
doi: 10.1021/jacs.9b00241
pubmed: 30942582
pmcid: 30942582
Guo, Y.-Y. et al. Molecular mechanism of azoxy bond formation for azoxymycins biosynthesis. Nat. Commun. 10, 1–9 (2019).
doi: 10.1038/s41467-018-07882-8
Baunach, M., Ding, L., Bruhn, T., Bringmann, G. & Hertweck, C. Regiodivergent N-C and N-N aryl coupling reactions of indoloterpenes and cycloether formation mediated by a single bacterial flavoenzyme. Angew. Chem. Int. Ed. 52, 9040–9043 (2013).
doi: 10.1002/anie.201303733
Zhang, Q. et al. Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification. Chem. Sci. 8, 5067–5077 (2017).
doi: 10.1039/C7SC01182B
pubmed: 28970893
pmcid: 28970893
Ng, T. L. et al. The L-alanosine gene cluster encodes a pathway for diazeniumdiolate biosynthesis. ChemBioChem https://doi.org/10.1002/cbic.201900565 (2019).
doi: 10.1002/cbic.201900565
pubmed: 31643127
pmcid: 31643127
Wang, M., Niikura, H., He, H.-Y., Daniel-Ivad, P. & Ryan, K. Biosynthesis of the nitrogen-nitrogen bond-containing L-alanosine. Angew. Chem. Int. Ed. https://doi.org/10.1002/anie.201913458 (2019).
doi: 10.1002/anie.201913458
Twigg, F. F. et al. Identifying the biosynthetic gene cluster for triacsins with an N-hydroxytriazene moiety. ChemBioChem 20, 1145–1149 (2019).
doi: 10.1002/cbic.201800762
pubmed: 30589194
pmcid: 30589194
Hirasawa, K. & Isono, K. Formation of 8-azaguanine from guanine by Streptomyces albus. J. Antibiot. 31, 628–629 (1978).
doi: 10.7164/antibiotics.31.628
pubmed: 681246
pmcid: 681246
Gräwert, T., Fischer, M. & Bacher, A. Structures and reaction mechanisms of GTP cyclohydrolases. IUBMB Life 65, 310–322 (2013).
doi: 10.1002/iub.1153
pubmed: 23457054
pmcid: 23457054
Crane, B. R., Sudhamsu, J. & Patel, B. A. Bacterial nitric oxide synthases. Annu. Rev. Biochem. 79, 445–470 (2010).
doi: 10.1146/annurev-biochem-062608-103436
pubmed: 20370423
pmcid: 20370423
Nathan, C. & Xie, Q. Nitric oxide synthases: roles, tolls, and controls. Cell 78, 915–918 (1994).
doi: 10.1016/0092-8674(94)90266-6
pubmed: 7522969
pmcid: 7522969
Kers, J. A. et al. Nitration of a peptide phytotoxin by bacterial nitric oxide synthase. Nature 429, 79–82 (2004).
doi: 10.1038/nature02504
pubmed: 15129284
pmcid: 15129284
Barry, S. M. et al. Cytochrome P450-catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis. Nat. Chem. Biol. 8, 814–816 (2012).
doi: 10.1038/nchembio.1048
pubmed: 22941045
pmcid: 22941045
Kurakawa, T. et al. Direct control of shoot meristem activity by a cytokinin-activating enzyme. Nature 445, 652–655 (2007).
doi: 10.1038/nature05504
pubmed: 17287810
pmcid: 17287810
Zhang, Y. E. et al. (p) ppGpp regulates a bacterial nucleosidase by an allosteric two-domain switch. Mol. Cell 74, 1239–1249 (2019).
doi: 10.1016/j.molcel.2019.03.035
pubmed: 31023582
pmcid: 31023582
Nagano, T. & Yoshimura, T. Bioimaging of nitric oxide. Chem. Rev. 102, 1235–1270 (2002).
doi: 10.1021/cr010152s
pubmed: 11942795
pmcid: 11942795
Bryan, N. S. & Grisham, M. B. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic. Bio. Med 43, 645–657 (2007).
doi: 10.1016/j.freeradbiomed.2007.04.026
Rebelo, J. et al. Biosynthesis of pteridines. reaction mechanism of GTP cyclohydrolase I. J. Mol. Biol. 326, 503–516 (2003).
doi: 10.1016/S0022-2836(02)01303-7
pubmed: 12559918
pmcid: 12559918
Frelin, O. et al. A directed-overflow and damage-control N-glycosidase in riboflavin biosynthesis. Biochem. J. 466, 137–145 (2015).
doi: 10.1042/BJ20141237
pubmed: 25431972
pmcid: 25431972
Blair, L. M. & Sperry, J. Natural products containing a nitrogen–nitrogen Bond. J. Nat. Prod. 76, 794–812 (2013).
doi: 10.1021/np400124n
pubmed: 23577871
pmcid: 23577871
Garg, R. P., Qian, X. L., Alemany, L. B., Moran, S. & Parry, R. J. Investigations of valanimycin biosynthesis: Elucidation of the role of seryl-tRNA. PNAS 105, 6543–6547 (2008).
doi: 10.1073/pnas.0708957105
pubmed: 18451033
pmcid: 18451033
Zhang, M. et al. Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction of C-nucleoside scaffolds. Appl. Environ. Microbiol. 86, e01971-19 (2019).
doi: 10.1128/AEM.01971-19
Fukumura, D., Kashiwagi, S. & Jain, R. K. The role of nitric oxide in tumour progression. Nat. Rev. Cancer 6, 521–534 (2006).
doi: 10.1038/nrc1910
pubmed: 16794635
pmcid: 16794635
Dawson, T. M. & Dawson, V. L. Nitric oxide synthase: role as a transmitter/mediator in the brain and endocrine system. Annu. Rev. Med. 47, 219–227 (1996).
doi: 10.1146/annurev.med.47.1.219
pubmed: 8712777
pmcid: 8712777
Bogdan, C. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol. 36, 161–178 (2015).
doi: 10.1016/j.it.2015.01.003
pubmed: 25687683
pmcid: 25687683
Tomita, H., Katsuyama, Y., Minami, H. & Ohnishi, Y. Identification and characterization of a bacterial cytochrome P450 monooxygenase catalyzing the 3-nitration of tyrosine in rufomycin biosynthesis. J. Biol. Chem. 292, 15859–15869 (2017).
doi: 10.1074/jbc.M117.791269
pubmed: 28774961
pmcid: 28774961
Ma, J. et al. Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents. Nat. Commun. 8, 1–10 (2017).
doi: 10.1038/s41467-016-0009-6
Sambrook, J. Molecular Cloning: A Laboratory Manual (CSHL Press, 2001).
Kieser, T. Practical Streptomyces Genetics (John Innes Foundation, 2000).
Gust, B., Challis, G. L., Fowler, K., Kieser, T. & Chater, K. F. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. PNAS 100, 1541–1546 (2003).
doi: 10.1073/pnas.0337542100
pubmed: 12563033
pmcid: 12563033
Du, Y.-L., Dalisay, D. S., Andersen, R. J. & Ryan, K. S. N-carbamoylation of 2,4-diaminobutyrate reroutes the outcome in padanamide biosynthesis. Chem. Biol. 20, 1002–1011 (2013).
doi: 10.1016/j.chembiol.2013.06.013
pubmed: 23911586
pmcid: 23911586