Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis

Nature Communications

Volumn 9, Issue 1, 2018, Pages

  Nakashima, Yu ^a   Mori, Takahiro ^a   Nakamura, Hitomi ^a   Awakawa, Takayoshi ^a   Hoshino, Shotaro ^a   Senda, Miki ^b   Senda, Toshiya ^b,c   Abe, Ikuro ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b INSTITUTE OF MATERIALS STRUCTURE SCIENCE   (Japan)

^c GRADUATE UNIVERSITY FOR ADVANCED STUDIES   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

MEROTERPENOID; NONHEME IRON PROTEIN; OXYGENASE; TERPENOID; UNCLASSIFIED DRUG; 2 OXOGLUTARIC ACID; AUSTINOL; MIXED FUNCTION OXIDASE; PREAUSTINOID A; TERPENE;

BIOACTIVITY; CATALYSIS; CHEMICAL REACTION; COMPARATIVE STUDY; ENGINEERING; ENZYME ACTIVITY; FUNGUS; MONOTERPENE; MUTATION; ULTRASTRUCTURE;

ARTICLE; ASPERGILLUS NIDULANS; BIOCATALYST; BIOSYNTHESIS; CONTROLLED STUDY; ENZYME ACTIVE SITE; ENZYME ENGINEERING; ENZYME KINETICS; ENZYME MECHANISM; ENZYME STRUCTURE; MUTAGENESIS; NONHUMAN; PENICILLIUM; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; CHEMISTRY; CLASSIFICATION; ENZYME SPECIFICITY; ENZYMOLOGY; GENETICS; METABOLISM; OXIDATION REDUCTION REACTION; PHYSIOLOGY;

EMERICELLA NIDULANS; PENICILLIUM BRASILIANUM;

ASPERGILLUS NIDULANS; CATALYTIC DOMAIN; KETOGLUTARIC ACIDS; MIXED FUNCTION OXYGENASES; NONHEME IRON PROTEINS; OXIDATION-REDUCTION; PENICILLIUM; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; TERPENES;

EID: 85040512187     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-017-02371-w     Document Type: Article

References (42)

1. Geris, R. & Simpson, T. J. Meroterpenoids produced by fungi. Nat. Prod. Rep. 26, 1063-1094 (2009).
2. Matsuda, Y. & Abe, I. Biosynthesis of fungal meroterpenoids. Nat. Prod. Rep. 33, 26-53 (2016).
3. Matsuda, Y., Awakawa, T., Mori, T. & Abe, I. Unusual chemistries in fungal meroterpenoid biosynthesis. Curr. Opin. Chem. Biol. 31, 1-7 (2016).
4. Cox, R. Oxidative rearrangements during fungal biosynthesis. Nat. Prod. Rep. 31, 1405-1424 (2014).
5. Hausinger, R. P. Fe(II)/α-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. Biol. 39, 21-68 (2004).
6. Nam, W., Lee, Y. M. & Fukuzumi, S. Tuning reactivity and mechanism in oxidation reactions by mononuclear nonheme Iron(IV)-oxo complexes. Acc. Chem. Res. 47, 1146-1154 (2014).
7. Price, J. C., Barr, E. W., Glass, T. E., Krebs, C. & Bollinger, J. M. Evidence for hydrogen abstraction from C1 of taurine by the high-spin Fe(IV) intermediate detected during oxygen activation by taurine:α-ketoglutarate dioxygenase (TauD). J. Am. Chem. Soc. 125, 13008-13009 (2003).
8. Flashman, E. & Schofield, C. J. The most versatile of all reactive intermediates? Nat. Chem. Biol. 3, 86-87 (2007).
9. Wu, L. F., Meng, S. & Tang, G. L. Ferrous iron and α-ketoglutarate-dependent dioxygenases in the biosynthesis of microbial natural products. Biochim. Biophys. Acta 1864, 453-470 (2016).
10. Cochrane, R. V. & Vederas, J. C. Highly selective but multifunctional oxygenases in secondary metabolism. Acc. Chem. Res. 47, 3148-3161 (2014).
11. Tang, M. C., Zou, Y., Watanabe, K., Walsh, C. T. & Tang, Y. Oxidative cyclization in natural product biosynthesis. Chem. Rev. 117, 5226-5333 (2017).
12. Itoh, T. et al. Identification of a key prenyltransferase involved in biosynthesis of the most abundant fungal meroterpenoids derived from 3,5-dimethylorsellinic acid. Chembiochem. 13, 1132-1135 (2012).
13. Matsuda, Y., Wakimoto, T., Mori, T., Awakawa, T. & Abe, I. Complete biosynthetic pathway of anditomin: nature's sophisticated synthetic route to a complex fungal meroterpenoid. J. Am. Chem. Soc. 136, 15326-15336 (2014).
14. Lo, H. C. et al. Two separate gene clusters encode the biosynthetic pathway for the meroterpenoids austinol and dehydroaustinol in Aspergillus nidulans. J. Am. Chem. Soc. 134, 4709-4720 (2012).
15. Matsuda, Y., Awakawa, T. & Abe, I. Reconstituted biosynthesis of fungal meroterpenoid andrastin A. Tetrahedron 69, 8199-8204 (2013).
16. Matsuda, Y. et al. Discovery of key dioxygenases that diverged the paraherquonin and acetoxydehydroaustin pathways in Penicillium brasilianum. J. Am. Chem. Soc. 138, 12671-12677 (2016).
17. Ishikawa, N. et al. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53, 12880-12884 (2014).
18. Matsuda, Y., Awakawa, T., Wakimoto, T. & Abe, I. Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis. J. Am. Chem. Soc. 135, 10962-10965 (2013).
19. Clifton, I. J. et al. Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins. J. Inorg. Biochem. 100, 644-669 (2006).
20. Yan, W. et al. Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme. Nature 527, 539-543 (2015).
21. Bräuer, A., Beck, P., Hintermann, L. & Groll, M. Structure of the dioxygenase AsqJ: mechanistic insights into a one-pot multistep quinolone antibiotic biosynthesis. Angew. Chem. Int. Ed. Engl. 55, 422-426 (2016).
22. CCP4, Collaborative Computational Project 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760-763 (1994).
23. Aik, W., McDonough, M. A., Thalhammer, A., Chowdhury, R. & Schofield, C. J. Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases. Curr. Opin. Struct. Biol. 22, 691-700 (2012).
24. Stierle, A., Stierle, D. & Decato, D. Crystal structure and absolute configuration of preaustinoid A1. Acta Crystallogr. E Crystallogr. Commun. 71, 596-597 (2015).
25. Stierle, D. et al. Berkeleyones and related meroterpenes from a deep water acid mine waste fungus that inhibit the production of interleukin 1-β from induced inflammasomes. J. Nat. Prod. 74, 2273-2277 (2011).
26. Que, L. Jr. One motif-many different reactions. Nat. Struct. Biol. 7, 182-184 (2000).
27. Oster, L. M. et al. Conformational flexibility of the C terminus with implications for substrate binding and catalysis revealed in a new crystal form of deacetoxycephalosporin C synthase. J. Mol. Biol. 343, 157-171 (2004).
28. Roach, P. L. et al. Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature 375, 700-704 (1995).
29. Roach, P. L. et al. Structure of isopenicillin N synthase complexed with substrate and the mechanism of penicillin formation. Nature 387, 827-830 (1997).
30. Hamed, R. B. et al. The enzymes of β-lactam biosynthesis. Nat. Prod. Rep. 30, 21-107 (2013).
31. Markolovic, S. et al. Structure-function relationships of human JmjC oxygenases-demethylases versus hydroxylases. Curr. Opin. Struct. Biol. 41, 62-72 (2016).
32. Firn, R. D. & Jones, C. G. Natural products - a simple model to explain chemical diversity. Nat. Prod. Rep. 20, 382-391 (2003).
33. Senda, M., Kishigami, S., Kimura, S. & Senda, T. Crystallization and preliminary X-ray analysis of the reduced Rieske-type [2Fe-2S] ferredoxin derived from Pseudomonas sp. strain KKS102. Acta Crystallogr. F 63, 311-314 (2007).
34. Rice, L. M., Earnest, T. N. & Brunger, A. T. Single-wavelength anomalous diffraction phasing revisited. Acta Crystallogr. D Biol. Crystallogr. 56, 1413-1420 (2000).
35. Kabsch, W. Xds. Acta Crystallogr. D Biol. Crystallogr. 66, 125-132 (2010).
36. Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D Biol. Crystallogr. 69, 1204-1214 (2013).
37. Terwilliger, T. C. et al. Decision-making in structure solution using Bayesian estimates of map quality: The PHENIX AutoSol wizard. Acta Crystallogr. D Biol. Crystallogr. 65, 582-601 (2009).
38. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010).
39. Terwilliger, T. C. et al. Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr. D Biol. Crystallogr. 64, 61-69 (2007).
40. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674 (2007).
41. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004).
42. Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D Biol. Crystallogr. 68, 352-367 (2012).