Xuechen Zhu, Rongbin Wang, Vilja Siitonen, Nemanja Vuksanovic, Nicholas R. Silvaggi, Charles E. Melançon III, and Mikko Metsä-Ketelä. ActVI-ORFA directs metabolic flux towards actinorhodin by preventing intermediate degradation. PLOS ONE. 2024 August 9. doi.org/10.1371/journal.pone.0308684
Benjamin Nji Wandi, Pedro Dinis, Vilja Siitonen, Gunter Schneider, Robert Schnell*, and Mikko Metsä-Ketelä*. Mechanism of Two-Component Mono-Oxygenases Involved in Anthracycline 1-Hydroxylation. ACS Catalysis. 2024 August 5. doi.org/10.1021/acscatal.4c02623
Aleksi Nuutila, Xiansha Xiao, Helga U. van der Heul, Gilles P. van Wezel, Pedro Dinis, Somayah S. Elsayed, and Mikko Metsä-Ketelä*. Divergence of Classical and C-Ring-Cleaved Angucyclines: Elucidation of Early Tailoring Steps in Lugdunomycin and Thioangucycline Biosynthesis. ACS Chemical Biology. 2024 April 26. doi.org/10.1021/acschembio.4c00082
Rongbin Wang, Benjamin Nji Wandi, Nora Schwartz, Jacob Hecht, Larissa Ponomareva, Kendall Paige, Alexis West, Kathryn Desanti, Jennifer Nguyen, Jarmo Niemi, Jon S. Thorson, Khaled A. Shaaban*, Mikko Metsä-Ketelä*, and S. Eric Nybo*. Diverse Combinatorial Biosynthesis Strategies for C–H Functionalization of Anthracyclinones. ACS Synthetic Biology. 2024 April 25. doi.org/10.1021/acssynbio.4c00043
Hulst MB, Zhang L, van der Heul HU, Du C, Elsayed SS, Koroleva A, Grocholski T, Metsä-Ketelä M, Neefjes JJC, van Wezel GP. Metabolic engineering of Streptomyces peucetius for biosynthesis of N,N-dimethylated anthracyclines. Frontiers in Bioengineering and Biotechnology. 2024 January 19. doi.org/10.3389/fbioe.2024.1363803
Elsayed SS, van der Heul HU, Xiao X, Nuutila A, Baars LR, Wu C, Metsä-Ketelä M, van Wezel GP. Unravelling key enzymatic steps in C-ring cleavage during angucycline biosynthesis. Communications Chemistry. 2023 December 18. doi.org/10.1038/s42004-023-01059-1
Baral B, Matroodi S, Siitonen V, Thapa K, Akhgari A, Yamada K, Nuutila A, Metsä-Ketelä M. Co-factor independent oxidases ncnN and actVA-3 are involved in the dimerization of benzoisochromanequinone antibiotics in naphthocyclinone and actinorhodin biosynthesis.FEMS Microbiology Letters. 2023 November 21. doi.org/10.1093/femsle/fnad123
Tirkkonen H, Brown KV, Niemczura M, Faudemer Z, Brown C, Ponomareva LV, Helmy YA, Thorson JS, Nybo SE, Metsä-Ketelä M, Shaaban KA. Engineering BioBricks for Deoxysugar Biosynthesis and Generation of New Tetracenomycins. ACS OMEGA. 2023 June 1. doi.org/10.1021/acsomega.3c02460
Artukka E, Schnell R, Palmu K, Rosenqvist P, Szodorai E, Niemi J, Virta P, Schneider G, Metsä-Ketelä M. Pseudouridine-Modifying Enzymes SapB and SapH Control Entry into the Pseudouridimycin Biosynthetic Pathway. ACS Chemical Biology. 2023 April 2. doi.org/10.1021/acschembio.2c00826
Dinis P, Tirkkonen H, Nji Wandi B, Siitonen V, Niemi J, Grocholski T, Metsä-Ketelä M. Evolution-inspired engineering of anthracycline methyltransferases. PNAS Nexus. 2023 Feb 28. doi.org/10.1093/pnasnexus/pgad009
Wang R, Nguyen J, Hecht J, Schqartz N, Brown KV, Ponomareva LV, Niemczura M, van Dissel D, van Wezel GP, Thorson JS, Metsä-Ketelä M, Shaaban KA, Nybo SE. A BioBricks Metabolic Engineering Platform for the Biosynthesis of Anthracyclinones in Streptomyces coelicolor. ACS Synthetic Biology. 2022 Nov 15. doi.org/10.1021/acssynbio.2c00498
Huang Y-H, Trapp V, Puro O, Mäkinen JJ, Metsä-Ketelä M, Wahl MC, Belogurov GA. Fluorogenic RNA aptamers to probe transcription initiation and co-transcriptional RNA folding by multi-subunit RNA polymerases. Methods in Enzymology. 2022 Aug 19. doi.org/10.1016/bs.mie.2022.07.010
Akhgari A, Baral B, Koroleva A, Siitonen V, Fewer DP, Melançon CE 3rd, Rahkila J, Metsä-Ketelä M. Single cell mutant selection for metabolic engineering of actinomycetes. Metabolic Engineering. 2022 July 7. doi.org/10.1016/j.ymben.2022.07.002
Rosenqvist P, Mäkinen JJ, Palmu K, Jokinen J, Prajapati RK, Korhonen HJ, Virta P, Belogurov GA, Metsä-Ketelä M. The role of the maleimide ring system on the structure-activity relationship of showdomycin. European Journal of Medicinal Chemistry. 2022 July 5. doi.org/10.1016/j.ejmech.2022.114342
Hulst MB, Grocholski T, Neefjes J.JC, van Wezel GP, Metsä-Ketelä M. Anthracyclines: biosynthesis, engineering and clinical applications. Natural Product Reports. 2021 December 24. doi.org/10.1039/D1NP00059D
Ahmed MN, Wahlsten M, Jokela J, Nees M, Stenman U-H, Alvarenga DO, Strandin T, Sivonen K, Poso A, Permi P, Metsä-Ketelä M, Koistinen H, Fewer DP. Potent Inhibitor of Human Trypsins from the Aeruginosin Family of Natural Products. ACS Chemical Biology. 2021 October 18. doi.org/10.1021/acschembio.1c00611
Hu Y, Zhou Q, Zhang Z, Pan H-X, Ilina Y, Metsä-Ketelä M, Igarashi Y, Tang G-L. Deciphering the Origin and Formation of Aminopyrrole Moiety in Kosinostatin Biosynthesis. Chinese Journal of Chemistry. 2021 September 1. doi.org/10.1002/cjoc.202100525
Baral B, Siitonen V, Laughlin M, Yamada K, Ilomäki M, Metsä-Ketelä M, Niemi J. Differential regulation of undecylprodigiosin biosynthesis in the yeast-scavenging Streptomyces strain MBK6. FEMS Microbiology Letters. 2021 April 21. doi:10.1093/femsle/fnab044
Mäkinen JJ, Shin Y, Vieras E, Virta P, Metsä-Ketelä M, Murakami KS, Belogurov GA. The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases. Nature Communications. 2021 February 4. doi:10.1038/s41467-021-21005-w
Zhu X, Siitonen V, Melançon CE 3rd, Metsä-Ketelä M. Biosynthesis of Diverse Type II Polyketide Core Structures in Streptomyces coelicolor M1152. ACS Synthetic Biology. 2021 January 20. doi:10.1021/acssynbio.0c00482
Brown KV, Nji Wandi B, Metsä-Ketelä M, Nybo SE. Pathway Engineering of Anthracyclines: Blazing Trails in Natural Product Glycodiversification. The Journal of Organic Chemistry. 2020 September 16. doi:10.1021/acs.joc.0c01863
Xiao X, Elsayed SS, Wu C, van der Huel HU, Metsä-Ketelä M, Du C, Prota AE, Chen C, Liu W, Guo R, Abrahams JP, van Wezel GP. Functional and Structural Insights into a Novel Promiscuous Ketoreductase of the Lugdunomycin Biosynthetic Pathwway. ACS Chemical Biology. 2020 August 25. doi: 10.1021/acschembio.0c00564
Vuksanovic N, Zhu X, Serrano DA, Siitonen V, Metsä-Ketelä M, Melançon CE 3rd, Silvaggi NR. Structural characterization of three noncanonical NTF2-like superfamily proteins: implications for polyketide biosynthesis. Acta Crystallogr F Struct Biol Commun. 2020 August 1. doi: 10.1107/S2053230X20009814
Matroodi S, Siitonen V, Baral B, Yamada K, Akhgari A, Metsä-Ketelä M. Genotyping-Guided Discovery of Persiamycin A from Sponge-Associated Halophilic Streptomonospora sp. PA3. Frontiers in Microbiology. 2020 June 9. doi: 10.3389/fmicb.2020.01237
Fewer DP, Metsä-Ketelä M. A pharmaceutical model for the molecular evolution of microbial natural products. FEBS J. 2019 November 5. doi: 10.1111/febs.15129
Nji Wandi B, Siitonen V, Palmu K, Metsä-Ketelä M. The Rieske Oxygenase SnoT Catalyzes 2′′‐Hydroxylation of L‐Rhodosamine in Nogalamycin Biosynthesis. ChemBioChem. 2020 June 17. doi: 10.1002/cbic.202000229
Nji Wandi B, Siitonen V, Dinis P, Vukic V, Salminen TA, Metsä-Ketelä M. Evolution-guided engineering of non-heme iron enzymes involved in nogalamycin biosynthesis. FEBS J. 2019 December 26. doi: 10.1111/febs.15192
Prajapati RK, Rosenqvist P, Palmu K, Mäkinen JJ, Malinen AM, Virta P, Metsä-Ketelä M, Belogurov GA. Oxazinomycin arrests RNA polymerase at the polythymidine sequences. Nucleic Acids Research. 2019 September 9. doi: 10.1093/nar/gkz782
Yamada K, Koroleva A, Laughlin M, Oksanen N, Akhgari A, Safronova V, Yakovleva E, Kolodyaznaya V, Buldakova T, Metsä-Ketelä M. Characterization and overproduction of cell-associated cholesterol oxidase ChoD from Streptomyces lavendulae YAKB-15. Scientific Reports. 2019 August 14. doi: 10.1038/s41598-019-48132-1.
Rosenqvist P, Palmu K, Prajapati R, Yamada K, Niemi J, Belogurov G, Mestä-Ketelä M, Virta P. Characterization of C-nucleoside Antimicrobials from Streptomyces albus DSM 40763: Strepuridin is Pseudouridimycin. Scientific Reports. 2019 June 20. doi: 10.1038/s41598-019-45375-w.
Grocholski T, Yamada K, Sinkkonen J, Tirkkonen H, Niemi J, Metsä-Ketelä M. Evolutionary Trajectories for the Functional Diversification of Anthracycline Methyltransferases. ACS Chemical Biology. 2019 Apr 23. doi: 10.1021/acschembio.9b00238.
Dinis P, Nji Wandi B, Grocholski T, Metsä-Ketelä M. Chimeragenesis for Biocatalysis. Advances in Enzyme Technology. 2019. doi: 10.1016/B978-0-444-64114-4.00014-5
Baral B, Akhgari A, Metsä-Ketelä M. Activation of microbial secondary metabolic pathways: Avenues and challenges. Synthetic and Systems Biotechnology. 2018 September 4. doi: 10.1016/j.synbio.2018.09.001.
Siitonen V, Nji Wandi B, Törmänen AP, Metsä-Ketelä M. Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R. ACS Chemical Biology. 2018 Aug 16. doi: 10.1021/acschembio.8b00658.
Metsä-Ketelä M, Schneider G. Nonheme Fe (II) and α‐Ketoglutarate‐Dependent Carbocyclase
SnoK and Epimerase SnoN. Encyclopedia of Inorganic and Bioinorganic Chemistry, 1-11. 2018
Metsä-Ketelä M. Evolution inspired engineering of antibiotic biosynthesis enzymes.
Org Biomol Chem. 2017 Apr 25. doi: 10.1039/C7OB00189D.
Palmu K, Rosenqvist P, Thapa K, Ilina Y, Siitonen V, Baral B, Mäkinen J, Belogurov G,
Virta P, Niemi J, Metsä-Ketelä M. Discovery of the Showdomycin Gene Cluster from
Streptomyces showdoensis ATCC 15227 Yields Insight into the Biosynthetic Logic of
C-Nucleoside Antibiotics. ACS Chem Biol. 2017 Apr 18. doi: 10.1021/acschembio.7b00078.
Siitonen V, Räty K, Metsä-Ketelä M. Laboratory course on Streptomyces genetics
and secondary metabolism. Biochem Mol Biol Educ. 2016 Sep 10;44(5):492-9. doi:
10.1002/bmb.20970. PubMed PMID: 27192442.
Siitonen V, Selvaraj B, Niiranen L, Lindqvist Y, Schneider G, Metsä-Ketelä M.
Divergent non-heme iron enzymes in the nogalamycin biosynthetic pathway. Proc
Natl Acad Sci U S A. 2016 May 10;113(19):5251-6. doi: 10.1073/pnas.1525034113.
PubMed PMID: 27114534; PubMed Central PMCID: PMC4868444.
Jackson DR, Yu X, Wang G, Patel AB, Calveras J, Barajas JF, Sasaki E,
Metsä-Ketelä M, Liu HW, Rohr J, Tsai SC. Insights into Complex Oxidation during
BE-7585A Biosynthesis: Structural Determination and Analysis of the Polyketide
Monooxygenase BexE. ACS Chem Biol. 2016 Apr 15;11(4):1137-47. doi:
10.1021/acschembio.5b00913. PubMed PMID: 26813028; PubMed Central PMCID:
PMC4902875.
Medema MH, Kottmann R, Yilmaz P, Cummings M, Biggins JB, Blin K, de Bruijn I,
Chooi YH, Claesen J, Coates RC, Cruz-Morales P, Duddela S, Düsterhus S, Edwards
DJ, Fewer DP, Garg N, Geiger C, Gomez-Escribano JP, Greule A, Hadjithomas M,
Haines AS, Helfrich EJ, Hillwig ML, Ishida K, Jones AC, Jones CS, Jungmann K,
Kegler C, Kim HU, Kötter P, Krug D, Masschelein J, Melnik AV, Mantovani SM,
Monroe EA, Moore M, Moss N, Nützmann HW, Pan G, Pati A, Petras D, Reen FJ,
Rosconi F, Rui Z, Tian Z, Tobias NJ, Tsunematsu Y, Wiemann P, Wyckoff E, Yan X,
Yim G, Yu F, Xie Y, Aigle B, Apel AK, Balibar CJ, Balskus EP, Barona-Gómez F,
Bechthold A, Bode HB, Borriss R, Brady SF, Brakhage AA, Caffrey P, Cheng YQ,
Clardy J, Cox RJ, De Mot R, Donadio S, Donia MS, van der Donk WA, Dorrestein PC,
Doyle S, Driessen AJ, Ehling-Schulz M, Entian KD, Fischbach MA, Gerwick L,
Gerwick WH, Gross H, Gust B, Hertweck C, Höfte M, Jensen SE, Ju J, Katz L,
Kaysser L, Klassen JL, Keller NP, Kormanec J, Kuipers OP, Kuzuyama T, Kyrpides
NC, Kwon HJ, Lautru S, Lavigne R, Lee CY, Linquan B, Liu X, Liu W, Luzhetskyy A,
Mahmud T, Mast Y, Méndez C, Metsä-Ketelä M, Micklefield J, Mitchell DA, Moore BS,
Moreira LM, Müller R, Neilan BA, Nett M, Nielsen J, O’Gara F, Oikawa H, Osbourn
A, Osburne MS, Ostash B, Payne SM, Pernodet JL, Petricek M, Piel J, Ploux O,
Raaijmakers JM, Salas JA, Schmitt EK, Scott B, Seipke RF, Shen B, Sherman DH,
Sivonen K, Smanski MJ, Sosio M, Stegmann E, Süssmuth RD, Tahlan K, Thomas CM,
Tang Y, Truman AW, Viaud M, Walton JD, Walsh CT, Weber T, van Wezel GP, Wilkinson
B, Willey JM, Wohlleben W, Wright GD, Ziemert N, Zhang C, Zotchev SB, Breitling
R, Takano E, Glöckner FO. Minimum Information about a Biosynthetic Gene cluster.
Nat Chem Biol. 2015 Sep;11(9):625-31. doi: 10.1038/nchembio.1890. PubMed PMID:
26284661.
Grocholski T, Dinis P, Niiranen L, Niemi J, Metsä-Ketelä M. Divergent
evolution of an atypical S-adenosyl-l-methionine-dependent monooxygenase involved
in anthracycline biosynthesis. Proc Natl Acad Sci U S A. 2015 Aug
11;112(32):9866-71. doi: 10.1073/pnas.1501765112. PubMed PMID: 26216966; PubMed
Central PMCID: PMC4538628.
Oja T, San Martin Galindo P, Taguchi T, Manner S, Vuorela PM, Ichinose K,
Metsä-Ketelä M, Fallarero A. Effective Antibiofilm Polyketides against
Staphylococcus aureus from the Pyranonaphthoquinone Biosynthetic Pathways of
Streptomyces Species. Antimicrob Agents Chemother. 2015 Oct;59(10):6046-52. doi:
10.1128/AAC.00991-15. PubMed PMID: 26195520; PubMed Central PMCID: PMC4576117.
Guo F, Xiang S, Li L, Wang B, Rajasärkkä J, Gröndahl-Yli-Hannuksela K, Ai G,
Metsä-Ketelä M, Yang K. Targeted activation of silent natural product
biosynthesis pathways by reporter-guided mutant selection. Metab Eng. 2015
Mar;28:134-42. doi: 10.1016/j.ymben.2014.12.006. PubMed PMID: 25554073.
Patrikainen P, Niiranen L, Thapa K, Paananen P, Tähtinen P, Mäntsälä P, Niemi
J, Metsä-Ketelä M. Structure-based engineering of angucyclinone 6-ketoreductases.
Chem Biol. 2014 Oct 23;21(10):1381-91. doi: 10.1016/j.chembiol.2014.07.017.
PubMed PMID: 25200607.
Thapa K, Oja T, Metsä-Ketelä M. Molecular evolution of the bacterial
pseudouridine-5′-phosphate glycosidase protein family. FEBS J. 2014
Oct;281(19):4439-49. doi: 10.1111/febs.12950. PubMed PMID: 25081867.
Ueberschaar N, Xu Z, Scherlach K, Metsä-Ketelä M, Bretschneider T, Dahse HM,
Görls H, Hertweck C. Synthetic remodeling of the chartreusin pathway to tune
antiproliferative and antibacterial activities. J Am Chem Soc. 2013 Nov
20;135(46):17408-16. doi: 10.1021/ja4080024. PubMed PMID: 24143864.
Vuorinen AL, Kalpio M, Linderborg KM, Kortesniemi M, Lehto K, Niemi J, Yang
B, Kallio HP. Coordinate changes in gene expression and triacylglycerol
composition in the developing seeds of oilseed rape (Brassica napus) and turnip
rape (Brassica rapa). Food Chem. 2014 Feb 15;145:664-73. doi:
10.1016/j.foodchem.2013.08.108. PubMed PMID: 24128529.
Blauenburg B, Oja T, Klika KD, Metsä-Ketelä M. Chemoenzymatic synthesis of
novel C-ribosylated naphthoquinones. ACS Chem Biol. 2013 Nov 15;8(11):2377-82.
doi: 10.1021/cb400384c. PubMed PMID: 24015959.
Metsä-Ketelä M, Oja T, Taguchi T, Okamoto S, Ichinose K. Biosynthesis of
pyranonaphthoquinone polyketides reveals diverse strategies for enzymatic
carbon-carbon bond formation. Curr Opin Chem Biol. 2013 Aug;17(4):562-70. doi:
10.1016/j.cbpa.2013.06.032. Review. PubMed PMID: 23886982.
Paananen P, Patrikainen P, Kallio P, Mäntsälä P, Niemi J, Niiranen L,
Metsä-Ketelä M. Structural and functional analysis of angucycline C-6
ketoreductase LanV involved in landomycin biosynthesis. Biochemistry. 2013 Aug
6;52(31):5304-14. doi: 10.1021/bi400712q. PubMed PMID: 23848284.
Kallio P, Patrikainen P, Belogurov GA, Mäntsälä P, Yang K, Niemi J,
Metsä-Ketelä M. Tracing the evolution of angucyclinone monooxygenases: structural
determinants for C-12b hydroxylation and substrate inhibition in PgaE.
Biochemistry. 2013 Jul 2;52(26):4507-16. doi: 10.1021/bi400381s. PubMed PMID:
23731237.
Taguchi T, Yabe M, Odaki H, Shinozaki M, Metsä-Ketelä M, Arai T, Okamoto S,
Ichinose K. Biosynthetic conclusions from the functional dissection of oxygenases
for biosynthesis of actinorhodin and related Streptomyces antibiotics. Chem Biol.
2013 Apr 18;20(4):510-20. doi: 10.1016/j.chembiol.2013.03.007. PubMed PMID:
23601640.
Oja T, Niiranen L, Sandalova T, Klika KD, Niemi J, Mäntsälä P, Schneider G,
Metsä-Ketelä M. Structural basis for C-ribosylation in the alnumycin A
biosynthetic pathway. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1291-6. doi:
10.1073/pnas.1207407110. PubMed PMID: 23297194; PubMed Central PMCID: PMC3557020.
Claesson M, Siitonen V, Dobritzsch D, Metsä-Ketelä M, Schneider G. Crystal
structure of the glycosyltransferase SnogD from the biosynthetic pathway of
nogalamycin in Streptomyces nogalater. FEBS J. 2012 Sep;279(17):3251-63. doi:
10.1111/j.1742-4658.2012.08711.x. PubMed PMID: 22804797.
Patrikainen P, Kallio P, Fan K, Klika KD, Shaaban KA, Mäntsälä P, Rohr J,
Yang K, Niemi J, Metsä-Ketelä M. Tailoring enzymes involved in the biosynthesis
of angucyclines contain latent context-dependent catalytic activities. Chem Biol.
2012 May 25;19(5):647-55. doi: 10.1016/j.chembiol.2012.04.010. PubMed PMID:
22633416; PubMed Central PMCID: PMC3361699.
Siitonen V, Blauenburg B, Kallio P, Mäntsälä P, Metsä-Ketelä M. Discovery of
a two-component monooxygenase SnoaW/SnoaL2 involved in nogalamycin biosynthesis.
Chem Biol. 2012 May 25;19(5):638-46. doi: 10.1016/j.chembiol.2012.04.009. PubMed
PMID: 22633415.
Oja T, Klika KD, Appassamy L, Sinkkonen J, Mäntsälä P, Niemi J, Metsä-Ketelä
M. Biosynthetic pathway toward carbohydrate-like moieties of alnumycins contains
unusual steps for C-C bond formation and cleavage. Proc Natl Acad Sci U S A. 2012
Apr 17;109(16):6024-9. doi: 10.1073/pnas.1201530109. PubMed PMID: 22474343;
PubMed Central PMCID: PMC3341043.
Grocholski T, Oja T, Humphrey L, Mäntsälä P, Niemi J, Metsä-Ketelä M.
Characterization of the two-component monooxygenase system AlnT/AlnH reveals
early timing of quinone formation in alnumycin biosynthesis. J Bacteriol. 2012
Jun;194(11):2829-36. doi: 10.1128/JB.00228-12. PubMed PMID: 22467789; PubMed
Central PMCID: PMC3370643.
Blauenburg B, Metsä-Ketelä M, Klika KD. Formation of
5-Hydroxy-3-methoxy-1,4-naphthoquinone and 8-Hydroxy-4-methoxy-1,2-naphthoquinone
from Juglone. ISRN Org Chem. 2012 Sep 23;2012:274980. doi: 10.5402/2012/274980.
PubMed PMID: 24052839; PubMed Central PMCID: PMC3767210.
Updated: August 2024