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Institute
Acharya, Shreyasi ; Adamová, Dagmar ; Adler, Alexander ; Adolfsson, Jonatan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Ahuja, Ishaan ; Akbar, Zaenal ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Ali, Yasir ; Alici, Andrea ; Alizadehvandchali, Negin ; Alkin, Anton ; Alme, Johan ; Alocco, Giacomo ; Alt, Torsten ; Altsybeev, Igor ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Dimitra ; Andronic, Anton ; Anguelov, Venelin ; Antinori, Federico ; Antonioli, Pietro ; Chandra, Anuj ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Aziz, Sizar ; Azmi, Mohd Danish ; Badalà, Angela ; Baek, Yong Wook ; Bai, Xiaozhi ; Bailhache, Raphaëlle ; Bailung, Yoshini ; 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Kim, Beomkyu ; Kim, Chong ; Kim, Dong Jo ; Kim, Eun Joo ; Kim, Jaehyun ; Kim, Jinsook ; Kim, Jiyoung ; Kim, Junlee ; Kim, Minjung ; Kim, Se Yong ; Kim, Taejun ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Kitowski, Jacek Pawel ; Klay, Jennifer Lynn ; Klein, Jochen ; Klein, Spencer Robert ; Klein-Bösing, Christian ; Kleiner, Matthias ; Klemenz, Thomas ; Kluge, Alexander ; Knospe, Anders Garritt ; Kobdaj, Chinorat ; Kollegger, Thorsten ; Kondratyev, Andrey ; Kondratyeva, Natalia ; Kondratyuk, Evgeny ; König, Joshua Leon ; Königstorfer, Stephan Alexander ; Konopka, Piotr Jan ; Kornakov, Georgy ; Koryciak, Sebastian Dominik ; Kotliarov, Artem ; Kovalenko, Oleksandr ; Kovalenko, Vladimir ; Kowalski, Marek ; Králik, Ivan ; Kravčáková, Adela ; Kreis, Lukas ; Krivda, Marian ; Krizek, Filip ; Krizkova Gajdosova, Katarina ; Kroesen, Martin ; Krüger, Mario ; Krupová, Diana Maria ; Kryshen, Evgeny ; Krzewicki, Mikolaj ; Kucera, Vit ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; 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Luparello, Grazia ; Ma, Yu-Gang ; Maevskaya, Alla ; Mager, Magnus ; Mahmoud, Tariq ; Maire, Antonin ; Malaev, Mikhail ; Malik, Nasir Mehdi ; Malik, Qasim Waheed ; Malik, Salman Khurshid ; Malinina, Liudmila ; Mal'Kevich, Dmitry ; Mallick, Dukhishyam ; Mallick, Neelkamal ; Mandaglio, Giuseppe ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Marin, Ana Maria ; Markert, Christina ; Marquard, Marco ; Martin, Nicole Alice ; Martinengo, Paolo ; Martinez, Jacobb Lee ; Martínez Hernández, Mario Iván ; Martínez Garcia, Ginés ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; Massacrier, Laure Marie ; Mastroserio, Annalisa ; Mathis, Andreas Michael ; Matonoha, Oliver ; Matuoka, Paula Fernanda Toledo ; Matyja, Adam Tomasz ; Mayer, Christoph ; Lafuente Mazuecos, Antonio ; Mazzaschi, Francesco ; Mazzilli, Marianna ; Mdhluli, Joyful Elma ; Mechler, Adrian Florin ; Melikyan, Yury ; Menchaca-Rocha, Arturo Alejandro ; Meninno, Elisa ; Sasikumar Menon, Anjaly ; Meres, Michal ; Mhlanga, Sibaliso ; Miake, Yasuo ; Micheletti, Luca ; Migliorin, Lucrezia Camilla ; Mihaylov, Dimitar ; Mikhaylov, Konstantin ; Mishra, Aditya Nath ; Miśkowiec, Dariusz Czesław ; Modak, Abhi ; Mohanty, Auro Prasad ; Mohanty, Bedangadas ; Khan, Mohammed Mohisin ; Molander, Mikael Andreas ; Moravcova, Zuzana ; Mordasini, Cindy ; Godoy, Denise Aparecida Moreira de ; Morozov, Igor ; Morsch, Andreas ; Mrnjavac, Teo ; Muccifora, Valeria ; Mudnic, Eugen ; Mühlheim, Daniel ; Muhuri, Sanjib ; Mulligan, James Declan ; Mulliri, Alice ; Gameiro Munhoz, Marcelo ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myrcha, Julian Wojciech ; Naik, Bharati ; Nair, Rahul Ramachandran ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Nassirpour, Adrian Fereydon ; Nath, Abhishek ; Nattrass, Christine ; Neagu, Alexandra ; Negru, Adrian-Eduard ; Nellen, Lukas ; Nesbo, Simon Voigt ; Nešković, Gvozden ; Nesterov, Dmitrii ; Nielsen, Borge Svane ; Nielsen, Emil Gorm ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Noh, Seoyoung ; Nomokonov, Petr V. ; Norman, Jaime ; Novitzky, Norbert ; Nowakowski, Piotr ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Ogino, Masanori ; Ohlson, Alice ; Okorokov, Vitaly A. ; Oleniacz, Janusz ; Silva, Antonio Carlos Oliveira da ; Oliver, Michael Henry ; Önnerstad, Anna ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Osako, Takumi ; Oskarsson, Anders Nils Erik ; Otwinowski, Jacek Tomasz ; Oya, Motomi ; Oyama, Ken ; Pachmayer, Yvonne C. ; Padhan, Sonali ; Pagano, Davide ; Paic, Guy ; Palasciano, Antonio ; Pan, Jinjin ; Panebianco, Stefano Matthias ; Park, Jonghan ; Parkkila, Jasper Elias ; Pathak, Surya Prakash ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pereira, Luis Gustavo ; Pereira da Costa, Hugo Denis Antonio ; Peresunko, Dmitry Yurevich ; Mesa Perez, Guillermo ; Perrin, Sébastien ; Pestov, Yury N. ; Petráček, Vojtech ; Petrovici, Mihai A. ; Pezzi, Rafael Peretti ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pinto, Chiara ; Pisano, Silvia ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Poghosyan, Martin G. ; Polishchuk, Boris ; Politano, Stefano ; Poljak, Nikola ; Pop, Amalia ; Porteboeuf, Sarah Julie ; Porter, R. 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Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmier, Austin Robert ; Schotter, Romain ; Schukraft, Jürgen ; Schwarz, Kilian Eberhard ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jin Joo ; Serebryakov, Dmitry ; Šerkšnytė, Laura ; Sevcenco, Adrian ; Shaba, Tebogo Joyce ; Shabanov, Arseniy ; Shabetai, Alexandre ; Shahoyan, Ruben ; Shaikh, Wadut ; Shangaraev, Artem ; Sharma, Anjali ; Sharma, Himanshu ; Sharma, Meenakshi ; Sharma, Natasha ; Sharma, Sheetal ; Sharma, Upasana ; Shatat, Afnan ; Sheibani, Oveis ; Shigaki, Kenta ; Hachiya Shimomura, Maya ; Shirinkin, Sergey ; Shou, Qiye ; Sibiryak, Yury ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Silva, Tiago Fiorini da ; Silvermyr, David Olle Rickard ; Simantathammakul, Tawanchat ; Simonetti, Giuseppe ; Singh, Bhawani ; Singh, Ranbir ; Singh, Randhir ; Singh, Ravindra ; Singh, Vivek ; Singhal, Vikas ; 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Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zhalov, Mikhail ; Zhang, Biao ; Zhang, Song ; Zhang, Xiaoming ; Zhang, Yifei ; Zherebchevskii, Vladimir ; Yu, Zhi ; Zhigareva, Natalia ; Zhou, Daicui ; Zhou, You ; Zhu, Jianhui ; Zhu, Ya ; Zinovjev, Gennady M. ; Zurlo, Nicola
The production of prompt Λ+c baryons at midrapidity (|y|<0.5) was measured in central (0-10%) and mid-central (30-50%) Pb-Pb collisions at the center-of-mass energy per nucleon-nucleon pair sNN−−−√=5.02 TeV with the ALICE detector. The Λ+c production yield, the Λ+c/D0 production ratio, and the Λ+c nuclear modification factor RAA are reported. The results are more precise and more differential in transverse momentum (pT) and centrality with respect to previous measurements. The Λ+c/D0 ratio, which is enhanced with respect to the pp measurement for 4<pT<8 GeV/c, is described by theoretical calculations that model the charm-quark transport in the quark-gluon plasma and include hadronization via both coalescence and fragmentation mechanisms.
Acharya, Shreyasi ; Adamová, Dagmar ; Agarwal, Apar ; Aglieri Rinella, Gianluca ; Aglietta, Luca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Ahuja, Ishaan ; Akindinov, Alexander ; Akishina, Valentina ; Al-Turany, Mohammad ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Alici, Andrea ; Alizadehvandchali, Negin ; Alkin, Anton ; Alme, Johan ; Alocco, Giacomo ; Alt, Torsten ; Altamura, Anna Rita ; Altsybeev, Igor ; Alvarado Garcia, Jesús Ricardo ; Ramirez Alvarez, Cesar Omar ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Nicodemos ; Andronic, Anton ; Andronov, Evgeny ; Anguelov, Venelin ; Antinori, Federico ; Antonioli, Pietro ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arata, Carolina ; Arcelli, Silvia ; Arnaldi, Roberta ; Arneiro, Jhoao Gabriel Martins Campos Almeida ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Averyanov, Dmitry ; Azmi, Mohd Danish ; Baba, Hitoshi ; Badalà, Angela ; Bae, Joonsuk ; Baek, Yong Wook ; Bai, Xiaozhi ; Bailhache, Raphaëlle ; Bailung, Yoshini ; Bala, Renu ; Balbino, Alessandro ; Baldisseri, Alberto ; Balis, Bartosz ; Banerjee, Debjani ; Banoo, Zarina ; Barbasova, Veronika ; Barile, Francesco ; Barioglio, Luca ; Barlou, Maria ; Barman, Banajit ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barreau, Emilie Martine ; Ramillien Barret, Valerie ; Barreto De Oliveira Campos, Leonardo ; Bartels, Clara ; Barth, Klaus ; Bartsch, Esther ; Bastid, Nicole ; Basu, Sumit ; Batigne, Guillaume ; Battistini, Daniel ; Batyunya, Boris ; Bauri, Dibakar ; Bazo Alba, José Luis ; Bearden, Ian Gardner ; Beattie, Caitlin ; Becht, Pascal ; Behera, Debadatta ; Belikov, Iouri ; Bell Hechavarria, Ailec de la Caridad ; Bellini, Francesca ; Bellwied, Rene ; Belokurova, Svetlana ; Espinoza Beltran, Lucina Gabriela ; Vasquez Beltran, Yael Antonio ; Bencédi, Gyula ; Bensaoula, Adel ; Beolè, Stefania ; Berdnikov, Yaroslav ; Berdnikova, Anastasia ; Bergmann, Luisa ; Besoiu, Mihaela Gabriela ; Betev, Latchezar ; Bhaduri, Partha Pratim ; Bhasin, Anju ; Bhattacharjee, Buddhadeb ; Bianchi, Livio ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bigot, Alexandre Patrick ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Saikat ; Bize, Nicolas Luc ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blidaru, Mihail-Bogdan ; Bluhme, Nora ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bodova, Tea ; Bok, Jeongsu ; Boldizsar, Laszlo ; Bombara, Marek ; Bond, Peter Matthew ; Bonomi, Germano ; Borel, Herve ; Borissov, Alexander ; Borquez Carcamo, Andres Gerardo ; Botta, Elena ; El Mard Bouziani, Youssef ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broz, Michal ; Bruno, Giuseppe Eugenio ; Buchakchiev, Valentin Dimitrov ; Buckland, Matthew Daniel ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bühler, Paul ; Burmasov, Nazar ; Buthelezi, Edith Zinhle ; Bylinkin, Alexander ; Bysiak, Sebastian Adam ; Cabanillas Noris, Juan Carlos ; Torres Cabrera, Maria Fernanda ; Cai, Mengke ; Caines, Helen Louise ; Caliva, Alberto ; Calvo Villar, Ernesto ; Mejia Camacho, Juan Manuel ; Camerini, Paolo ; Canedo, Fabio de Moraes ; Weyhmiller, Sierra Lisa ; Carabas, Mihai ; Amatriain Carballo, Aitor ; Carnesecchi, Francesca ; Caron, Robin Albert Andre ; Abranches De Carvalho, Leopoldo ; Castillo Castellanos, Javier Ernesto ; Castoldi, Matteo ; Catalano, Fabio ; Cattaruzzi, Samuele ; Ceballos Sanchez, Cesar ; Cerri, Rebecca ; Chakaberia, Irakli ; Chakraborty, Pritam ; Chandra, Sinjini ; Chapeland, Sylvain ; Chartier, Marielle ; Chattopadhay, Souvik ; Chattopadhyay, Subhasis ; Chattopadhyay, Sukalyan ; Chen, Meiyi ; Cheng, Tiantian ; Cheshkov, Cvetan Valeriev ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Chizzali, Emma Sophia ; Cho, Jaeyoon ; Cho, Soyeon ; Chochula, Peter ; Chochulska, Zuzanna Anna ; Choudhury, Dhrubajyoti ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Ciacco, Mario ; Cicalò, Corrado ; Ciupek, Michael Rudolf ; Clai, Giulia ; Colamaria, Fabio Filippo ; Colburn, Jonathan Samuel ; Colella, Domenico ; Colocci, Manuel ; Concas, Matteo ; Conesa Balbastre, Gustavo ; Conesa del Valle, Zaida ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Coquet, Maurice ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Costanza, Susanna ; Cot, Corentin ; Crochet, Philippe ; Cruz Torres, Reynier ; Cui, Pengyao ; Czarnynoga, Maciej Marek ; Dainese, Andrea ; Dange, Gautam ; Danisch, Meike Charlotte ; Danu, Andrea ; Das, Prottay ; Das, Prottoy ; Das, Supriya ; Dash, Archita Rani ; Dash, Sadhana ; De Caro, Annalisa ; De Cataldo, Giacinto ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; De Marco, Nora ; De Martin, Chiara ; De Pasquale, Salvatore ; Deb, Rohaan ; Del Grande, Raffaele ; Dello Stritto, Luigi ; Deng, Wenjing ; Devereaux, Kyle Christian ; Dhankher, Preeti ; Di Bari, Domenico ; Di Mauro, Antonio ; Diab, Batoul ; Arteche Diaz, Raul ; Dietel, Thomas ; Ding, Yanchun ; Ditzel, Janik ; Divià, Roberto ; Djuvsland, Øystein ; Dmitrieva, Uliana ; Dobrin, Alexandru Florin ; Donigus, Benjamin ; Dubiński, Jan Michal ; Dubla, Andrea ; Dupieux, Pascal ; Dzalaiova, Natalia ; Eder, Tabea Maria ; Ehlers, Raymond James, III ; Eisenhut, Florian ; Ejima, Ren ; Elia, Domenico ; Erazmus, Barbara Ewa ; Ercolessi, Francesca ; Espagnon, Bruno ; Eulisse, Giulio ; Evans, David ; Evdokimov, Sergey ; Fabbietti, Laura ; Faggin, Mattia ; Faivre, Julien ; Fan, Feng ; Fan, Wenqing ; Fantoni, Alessandra ; Fasel, Markus ; Feliciello, Alessandro ; Feofilov, Grigori A. ; Fernández Téllez, Arturo ; Ferrandi De Oliveira, Lucas ; Bertran Ferrer, Marta ; Ferrero, Andrea ; Ferrero, Chiara ; Ferretti, Alessandro ; Feuillard, Victor Jose Gaston ; Filova, Vendulka ; Finogeev, Dmitry ; Fionda, Fiorella Maria Celeste ; Flatland, Erlend ; Flor, Fernando Antonio ; Flores, Amanda Nicole ; Foertsch, Siegfried Valentin ; Fokin, Ilya ; Fokin, Sergey ; Follo, Umberto ; Fragiacomo, Enrico ; Frajna, Eszter ; Fuchs, Ulrich ; Funicello, Nicola ; Furget, Christophe ; Furs, Artur ; Fusayasu, Takahiro ; Gaardhøje, Jens Jørgen ; Gagliardi, Martino ; Gago Medina, Alberto Martín ; Gahlaut, Tanu ; Duarte Galvan, Carlos ; Gangadharan, Dhevan Raja ; Ganoti, Paraskevi ; Garabatos Cuadrado, Jose Maria ; Martinez Garcia, Josue ; García Chávez, Tonatiuh ; Garcia-Solis, Edmundo Javier ; Gargiulo, Corrado ; Gasik, Piotr ; Gaur, Hari Mohan ; Gautam, Amrit ; Ducati, Maria Beatriz de Leone Gay ; Germain, Marie ; Gernhaeuser, Roman August ; Ghosh, Chandrasekhar ; Giacalone, Marco ; Gioachin, Giulia ; Giri, Sourav Kanti ; Giubellino, Paolo ; Giubilato, Piero ; Glaenzer, Aude Marie Camille ; Glässel, Peter ; Glimos, Ewa ; Goh, Daniel Jia Qin ; Gonzalez Sebastian, Victor Luis ; Gordeev, Pavel ; Gorgon, Marek Boguslaw ; Goswami, Kangkan ; Gotovac, Sven ; Grabski, Varlen ; Graczykowski, Łukasz Kamil ; Grecka, Ekaterina ; Grelli, Alessandro ; Grigoraș, Costin ; Grigoryev, Vladislav ; Grigoryan, Smbat ; Grosa, Fabrizio ; Große-Oetringhaus, Jan Fiete ; Grosso, Raffaele ; Grund, David ; Grünwald, Nadine Alice ; Garcia Guardiano, Gabriel ; Guernane, Rachid ; Guilbaud, Maxime Rene Joseph ; Gulbrandsen, Kristjan Herlache ; Karlsson Gumprecht, Jesper Jan Walter ; Gündem, Tuba ; Gunji, Taku ; Guo, Wenda ; Gupta, Anik ; Gupta, Ramni ; Gupta, Rashi ; Gwizdziel, Katarzyna ; Gyulai, Laszlo ; Hadjidakis, Cynthia Marie ; Haider, Fakhar Ul ; Haidlova, Sara ; Haldar, Mintu ; Hamagaki, Hideki ; Hamdi, Abdennacer ; Han, Younghoon ; Hanley, Brian Gerald ; Hannigan, Ryan ; Hansen, Joachim ; Haque, Md Rihan ; Harris, John William ; Harton, Austin Vincent ; Hartung, Michael Volker ; Hassan, Hadi ; Hatzifotiadou, Despina ; Hauer, Philip ; Havener, Laura Brittany ; Hellbär, Ernst ; Helstrup, Håvard ; Hemmer, Marvin ; Herman, Tomáš ; Hernandez, Sabrina Gabrielle ; Herrera Corral, Gerardo Antonio ; Herrmann, Sarah Nina Edwige ; Hetland, Kristin Fanebust ; Heybeck, Benedict ; Hillemanns, Hartmut ; Hippolyte, Boris ; Hoffmann, Felix Willi ; Hofman, Bas ; Hong, Geunhee ; Horst, Maximilian ; Horzyk, Adrian ; Hou, Yongzhen ; Hristov, Peter ; Huhn, Patrick ; Huhta, Laura Maria ; Humanic, Thomas J. ; Hutson, Alek ; Hutter, Dirk ; Hwang, Minyoung Chris ; Ilkaev, Radiy ; Inaba, Motoi ; Innocenti, Gian Michele ; Ippolitov, Mikhail ; Isakov, Artem ; Isidori, Tommaso ; Islam, Md Samsul ; Iurchenko, Semen ; Ivanov, Marian ; Ivanov, Marian ; Ivanov, Vladimir ; Iversen, Kaare Endrup ; Jablonski, Miroslaw ; Jacak, Barbara ; Jacazio, Nicolò ; Jacobs, Peter Martin ; Jadlovska, Slavka ; Jadlovsky, Jan ; Jaelani, Syaefudin ; Jahnke, Cristiane ; Jakubowska, Monika Joanna ; Janik, Malgorzata Anna ; Janson, Thomas ; Ji, Su-jeong ; Jia, Shihai ; Jiang, Tao ; Paz Jimenez, Alom Antonio ; Jonas, Florian ; Jones, Daniel Matthew ; Jowett, John M. ; Jung, Jerome ; Jung, Michael ; Junique, Antoine Jean-Simon ; Jusko, Anton ; Kaewjai, Jetnipit ; Kalinak, Peter ; Kalweit, Alexander Philipp ; Karasu Uysal, Ayben ; Karatović, David ; Karatzenis, Nikolaos ; Karavichev, Oleg V. ; Karavicheva, Tatiana L. ; Karpechev, Evgeny ; Karwowska, Maja Jadwiga ; Kebschull, Udo ; Keidel, Ralf ; Keil, Markus ; Ketzer, Bernhard ; Khade, Swapnesh Santosh ; Khan, Ahsan Mehmood ; Khan, Shaista ; Khanzadeev, Alexei ; Kharlov, Yury ; Khatun, Anisa ; Khuntia, Arvind ; Khuranova, Zhanna ; Kileng, Bjarte ; Kim, Beomkyu ; Kim, Chong ; Kim, Dong Jo ; Kim, Eun Joo ; Kim, Jaehyun ; Kim, Jiyoung ; Kim, Junlee ; Kim, Minjung ; Kim, Se Yong ; Kim, Taejun ; Kimura, Kento ; Kirkova, Aleksandrina ; Kirsch, Stefan ; Kisel, Ivan ; Kiselev, Sergej N. ; Kisiel, Adam Ryszard ; Kitowski, Jacek Pawel ; Klay, Jennifer Lynn ; Klein, Jochen ; Klein, Spencer Robert ; Klein-Bösing, Christian ; Kleiner, Matthias ; Klemenz, Thomas ; Kluge, Alexander ; Kobdaj, Chinorat ; Kohara, Ryotaro ; Kollegger, Thorsten ; Kondratyev, Andrey ; Kondratyeva, Natalia ; König, Joshua Leon ; Königstorfer, Stephan Alexander ; Konopka, Piotr Jan ; Kornakov, Georgy ; Korwieser, Maximilian ; Koryciak, Sebastian Dominik ; Koster, Cornelia ; Kotliarov, Artem ; Kovacic, Nino ; Kovalenko, Vladimir ; Kowalski, Marek ; Kozhuharov, Venelin Valeriev ; Kozlov, Grigory ; Králik, Ivan ; Kravčáková, Adela ; Krcal, Lubos ; Krivda, Marian ; Krizek, Filip ; Krizkova Gajdosova, Katarina ; Krug, Cristiano ; Krüger, Mario ; Krupová, Diana Maria ; Kryshen, Evgeny ; Kucera, Vit ; Kuhn, Christian Claude ; Kuijer, Paulus Gerardus ; Kumaoka, Takuya ; Kumar, Deekshit ; Kumar, Lokesh ; Kumar, Navneet ; Kumar, Shyam ; Kundu, Sourav ; Kurashvili, Podist ; Kurepin, Alexander ; Kurepin, Alexey B. ; Kuryakin, Alexey ; Kushpil, Svetlana ; Kuskov, Vladislav ; Kutyla, Monika ; Kuznetsov, Andrey ; Kweon, Min Jung ; Kwon, Youngil ; La Pointe, Sarah Louise ; La Rocca, Paola ; Lakrathok, Anantachai ; Lamanna, Massimo ; Landou, Aimeric Robin ; Langoy, Rune ; Larionov, Pavel ; Laudi, Elisa ; Lautner, Lukas ; Narcio Laveaga, Rafael Angel ; Lavicka, Roman ; Lea, Ramona ; Lee, Hyungjun ; Legrand, Iosif-charles ; Legras, Gauthier ; Lehrbach, Johannes ; Lejeune, Alexian Marc ; Lelek, Tomasz Marcin ; Lemmon, Roy Crawford ; Leon Monzon, Ildefonso ; Lesch, Marcel Markus ; Lesser, Ezra Douglas ; Lévai, Peter ; Li, Mingze ; Li, Xiaomei ; Liang-Gilman, Beatrice Eva ; Lien, Jørgen André ; Lietava, Roman ; Likmeta, Iris ; Lim, Bong-Hwi ; Lim, Sanghoon ; Lindenstruth, Volker ; Lindner, Amelia ; Lippmann, Christian ; Liu, Donghai ; Liu, Jian ; Setoue Liveraro, Gianni Shigeru ; Mckibben Lofnes, Ingrid ; Loizides, Constantinos ; Lokos, Sandor ; Lomker, Johanna ; Lopez, Xavier Bernard ; López Torres, Ernesto ; Lotteau, Clement ; Lu, Pengzhong ; Lu, Zhiyong ; Lugo, Fabiola Viridiana ; Luhder, Jens Robert ; Lunardon, Marcello ; Luparello, Grazia ; Ma, Yu-Gang ; Mager, Magnus ; Maire, Antonin ; Majerz, Emilia Maria ; Makariev, Martin Vasilev ; Malaev, Mikhail ; Malfattore, Giovanni ; Malik, Nasir Mehdi ; Malik, Qasim Waheed ; Malik, Salman Khurshid ; Malinina, Liudmila ; Mallick, Dukhishyam ; Mallick, Neelkamal ; Mandaglio, Giuseppe ; Mandal, Sushobhan Kumar ; Manea, Alexandru ; Manko, Vladislav ; Manso, Franck ; Manzari, Vito ; Mao, Yaxian ; Marcjan, Robert Waclaw ; Margagliotti, Giacomo Vito ; Margotti, Anselmo ; Marin, Ana Maria ; Markert, Christina ; Martinengo, Paolo ; Martínez Hernández, Mario Iván ; García Martínez, Ginés ; Martins Palhares, Maria Paula ; Masciocchi, Silvia ; Masera, Massimo ; Masoni, Alberto ; Massacrier, Laure Marie ; Massen, Olaf ; Mastroserio, Annalisa ; Matonoha, Oliver ; Mattiazzo, Serena ; Matyja, Adam Tomasz ; Lafuente Mazuecos, Antonio ; Mazzaschi, Francesco ; Mazzilli, Marianna ; Mdhluli, Joyful Elma ; Melikyan, Yury ; Paulino, Maria Monalisa de Melo ; Menchaca-rocha, Arturo Alejandro ; Munoz Mendez, Jesus Eduardo ; Meninno, Elisa ; Sasikumar Menon, Anjaly ; Menzel, Marius Wilm ; Meres, Michal ; Miake, Yasuo ; Micheletti, Luca ; Mihaylov, Dimitar Lubomirov ; Mikhaylov, Konstantin ; Minafra, Nicola ; Czeslaw Miskowiec, Dariusz ; Modak, Abhi ; Mohanty, Bedangadas ; Khan, Mohammed Mohisin ; Molander, Mikael Andreas ; Monira, Shirajum ; Mordasini, Cindy ; Moreira De Godoy Willems, Denise Aparecida ; Morozov, Igor ; Morsch, Andreas ; Mrnjavac, Teo ; Muccifora, Valeria ; Muhuri, Sanjib ; Mulligan, James Declan ; Mulliri, Alice ; Gameiro Munhoz, Marcelo ; Munzer, Robert Helmut ; Murakami, Hikari ; Murray, Sean ; Musa, Luciano ; Musinsky, Jan ; Myrcha, Julian Wojciech ; Naik, Bharati ; Nambrath, Anjali Ila ; Nandi, Basanta Kumar ; Nania, Rosario ; Nappi, Eugenio ; Nassirpour, Adrian Fereydon ; Nath, Abhishek ; Nath, Subhadeep ; Nattrass, Christine ; Naydenov, Momchil Nikolaev ; Neagu, Alexandra ; Negru, Adrian-eduard ; Nekrasova, Evgeniia ; Nellen, Lukas ; Nepeivoda, Roman ; Nese, Sigurd ; Nicassio, Nicola ; Nielsen, Borge Svane ; Nielsen, Emil Gorm ; Nikolaev, Sergey ; Nikulin, Sergey ; Nikulin, Vladimir ; Noferini, Francesco ; Noh, Seoyoung ; Nomokonov, Petr V. ; Norman, Jaime ; Novitzky, Norbert ; Nowakowski, Piotr ; Nyanin, Alexander ; Nystrand, Joakim Ingemar ; Oh, Saehanseul ; Ohlson, Alice ; Okorokov, Vitaly A. ; Oleniacz, Janusz ; Önnerstad, Anna ; Oppedisano, Chiara ; Ortiz Velasquez, Antonio ; Otwinowski, Jacek Tomasz ; Oya, Motomi ; Oyama, Ken ; Pachmayer, Yvonne C. ; Padhan, Sonali ; Pagano, Davide ; Paic, Guy ; Paisano Guzman, Sergio ; Palasciano, Antonio ; Panebianco, Stefano Matthias ; Park, Hanseo ; Park, Hyebin ; Park, Jonghan ; Parkkila, Jasper Elias ; Patley, Yash ; Patra, Rajendra Nath ; Paul, Biswarup ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pennisi, Michele ; Perciballi, Stefania ; Peresunko, Dmitry Yurevich ; Mesa Perez, Guillermo ; Pestov, Yury N. ; Petersen, Mikkel Tornhoj ; Petrov, Vitalii ; Petrovici, Mihai A. ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pinto, Chiara ; Pisano, Silvia ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Plociennik, Damian Kacper ; Poghosyan, Martin G. ; Polishchuk, Boris ; Politano, Stefano ; Poljak, Nikola ; Pop, Amalia ; Porteboeuf, Sarah Julie ; Pozdniakov, Valerii ; Yoval Pozos, Irandheny ; Pradhan, Kshitish Kumar ; Prasad, Sidharth Kumar ; Prasad, Suraj ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Pucillo, Sara ; Qiu, Shi ; Quaglia, Luca ; Ragoni, Simone ; Rai, Ananya ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rasa, Marika ; Räsänen, Sami Sakari ; Rath, Rutuparna ; Rauch, Max Philip ; Ravasenga, Ivan ; Read, Kenneth Francis ; Reckziegel, Christian ; Redelbach, Andreas Ralph ; Redlich, Krzysztof ; Reetz, Carolina Anna ; Regules Medel, Hector David ; Rehman, Attiq ur ; Reidt, Felix ; Reme-Ness, Haakon André ; Jakubcinova, Zuzana ; Reygers, Klaus ; Riabov, Andrei ; Riabov, Viktor ; Ricci, Riccardo ; Richter, Matthias ; Riedel, Anton Albert ; Riegler, Werner ; Riffero, Andrea Giovanni ; Ripoli, Cristina ; Ristea, Cătălin-Lucian ; Viqueira Rodriguez, Manuel ; Rodrı́guez Cahuantzi, Mario ; Rodríguez Ramírez, Saúl Aníbal ; Røed, Ketil ; Rogalev, Roman ; Rogochaya, Elena ; Rogoschinski, Tim Sebastian ; Rohr, David ; Röhrich, Dieter ; Rojas Torres, Solangel ; Rokita, Przemyslaw Stefan ; Romanenko, Gleb ; Ronchetti, Federico ; Dominguez Rosas, Edgar ; Rosłon, Krystian ; Rossi, Andrea ; Roy, Ankhi ; Roy, Subhadeep ; Rubini, Nicola ; Rudolph, Justus Arne ; Ruggiano, Daniela ; Rui, Rinaldo ; Russek, Paweł Grzegorz ; Russo, Roberto ; Rustamov, Anar ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej Krzysztof ; Ryu, Jaehyeok ; Rzęsa, Wioleta ; Sabiu, Bianca ; Sadovskiy, Sergey ; Sætre, Jon-are ; Šafařík, Karel ; Saha, Sumit Kumar ; Saha, Swati ; Sahoo, Bhagyarathi ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Dushmanta ; Sahu, Pradip Kumar ; Saini, Jogender ; Tropp, Klaudia ; Sakai, Shingo ; Panikkassery Salvan, Malavika ; Sambyal, Sanjeev Singh ; Samitz, Daniel ; Sanna, Isabella ; Saramela, Thiago Badaró ; Sarkar, Debojit ; Sarma, Pranjal ; Sarritzu, Valerio ; Mantovani Sarti, Valentina ; Sas, Mike Henry Petrus ; Sawan, Sawan ; Scapparone, Eugenio ; Schambach, Johann Joachim ; Scheid, Horst Sebastian ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schlepper, Felix ; Schmah, Alexander ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmier, Austin Robert ; Schotter, Romain ; Wilhelmi, Alexander ; Schukraft, Jürgen ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selina, Mariia ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jin Joo ; Serebryakov, Dmitry ; Serkin, Leonid ; Šerkšnytė, Laura ; Sevcenco, Adrian ; Shaba, Tebogo Joyce ; Shabetai, Alexandre ; Shahoyan, Ruben ; Shangaraev, Artem ; Sharma, Binti ; Sharma, Deependra ; Sharma, Himanshu ; Sharma, Meenakshi ; Sharma, Samarth ; Sharma, Sheetal ; Sharma, Upasana ; Shatat, Afnan ; Sheibani, Oveis ; Shigaki, Kenta ; Hachiya Shimomura, Maya ; Shin, Jaehyuck ; Shirinkin, Sergey ; Shou, Qiye ; Sibiryak, Yury ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Silva, Tiago Fiorini da ; Silvermyr, David Olle Rickard ; Simantathammakul, Tawanchat ; Simeonov, Radoslav ; Singh, Balwan ; Singh, Bhawani ; Singh, Kamaljeet ; Singh, Ranbir ; Singh, Randhir ; Singh, Ravindra ; Singh, Sweta ; Singh, Vivek ; Singhal, Vikas ; Sarkar-Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Skorodumovs, Georgijs ; Smirnov, Nikolai ; Snellings, Raimond ; Solheim, Emilie ; Song, Jihye ; Sonnabend, Christian ; Sonneveld, Jorine Mirjam ; Soramel, Francesca ; Soto-Hernandez, Analyce Bella ; Spijkers, Rik ; Sputowska, Iwona Anna ; Staa, Joey ; Stachel, Johanna ; Stan, Ionel ; Steffanic, Patrick John ; Stellhorn, Tim ; Stiefelmaier, Stephan ; Stocco, Diego ; Storehaug, Ida ; Strangmann, Nicolas Justus ; Stratmann, Peter ; Strazzi, Sofia ; Sturniolo, Alessandro ; Pliatskas Stylianidis, Christos ; Suaide, Alexandre Alarcon do Passo ; Suire, Christophe Pierre ; Sukhanov, Mikhail ; Šuljić, Miljenko ; Sultanov, Rishat ; Sumberia, Vikash ; Sumowidagdo, Suharyo ; Szarka, Imrich ; Szymkowski, Maciej ; Taghavi, Seyed Farid ; Taillepied, Guillaume ; Takahashi, Jun ; Tambave, Ganesh ; Tang, Siyu ; Tang, Zebo ; Tapia Takaki, Jesus Daniel ; Țăpuş, Nicolae ; Tarasovičová, Lucia Anna ; Tarzila, Madalina-gabriela ; Tassielli, Giovanni Francesco ; Tauro, Arturo ; Tavira Garcia, Andrea ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terlizzi, Livia ; Terrevoli, Cristina ; Thakur, Sanchari ; Thomas, Deepa ; Tikhonov, Anatoly ; Tiltmann, Nicolas ; Timmins, Anthony Robert ; Tkacik, Milan ; Tkacik, Tomas ; Toia, Alberica ; Tokumoto, Ryoka ; Tomassini, Sofia ; Tomohiro, Keisuke ; Topilskaya, Nataliya ; Toppi, Marco ; Valencia Torres, Victor ; Torres Ramos, Arianna Grisel ; Trifiro, Antonio ; Triloki, Triloki ; Triolo, Andrea Sofia ; Tripathy, Sushanta ; Tripathy, Tulika ; Trubnikov, Victor ; Trzaska, Wladyslaw Henryk ; Trzcinski, Tomasz Piotr ; Tsolanta, Christina ; Tu, Ran ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ullaland, Kjetil ; Ulukutlu, Berkin ; Uras, Antonio ; Urioni, Marta ; Usai, Gianluca ; Vala, Martin ; Valle, Nicolò ; Doremalen, Lennart Vincent Rogier van ; Leeuwen, Marco van ; Van Veen, Casper Arie ; Weelden, Roelof Jan Gijs van ; Vyvre, Pierre vande ; Varga, Dezsö ; Varga, Zoltán ; Vargas Torres, Paola ; Vasileiou, Maria ; Vasiliev, Andrey ; Vázquez Doce, Oton ; Vazquez Rueda, Omar ; Vechernin, Vladimir ; Vercellin, Ermanno ; Vergara Limon, Sergio ; Verma, Rahul ; Vermunt, Lucas Anne ; Vértesi, Róbert ; Verweij, Marta ; Vicković, Linda ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Villani, Anna ; Vinogradov, Alexander ; Virgili, Tiziano ; Virta, Maxim Mikael Olavi ; Vodopyanov, Alexander ; Völkel, Benedikt ; Völkl, Martin Andreas ; Voloshin, Sergei ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Vozniuk, Nikita ; Vrláková, Janka ; Wan, Jie ; Wang, Chunzheng ; Wang, Dongfang ; Wang, Yuanzhe ; Wang, Yubiao ; Wegrzynek, Adami Tadeusz ; Weiglhofer, Felix Thomas ; Wenzel, Sandro Christian ; Wessels, Johannes P. ; Wiechula, Jens ; Wikne, Jon ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy John ; Willems, Guido Alexander ; Windelband, Bernd ; Winn, Michael ; Wright, Josephina Rae ; Wu, Wenya ; Wu, Yitao ; Xiong, Zhenjun ; Xu, Ran ; Yadav, Ankur ; Yadav, Arun Kumar ; Yamaguchi, Yorito ; Yang, Shiming ; Yano, Satoshi ; Yeats, Emma Rose ; Yin, Zhongbao ; Yoo, In-Kwon ; Yoon, Jin Hee ; Yu, Hyeonjin ; Yuan, Shiming ; Yüncü, Alperen ; Zaccolo, Valentina ; Zampolli, Chiara ; Zhang, Mingyu ; Zanone, Federica ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zhalov, Mikhail ; Zhang, Biao ; Zhang, Chi ; Zhang, Liuyao ; Zhang, Maolin ; Zhang, Song ; Zhang, Xiaoming ; Zhang, Yifei ; Zhang, Zhen ; Zhao, Mingrui ; Zherebchevskii, Vladimir ; Yu, Zhi ; Zhou, Daicui ; Zhou, You ; Zhu, Jianhui ; Zhu, Senjie ; Zhu, Ya ; Zugravel, Stefan Cristi ; Zurlo, Nicola
The production cross section of inclusive isolated photons has been measured by the ALICE experiment at the CERN LHC in pp collisions at centre-of-momentum energy of s√=13 TeV collected during the LHC Run 2 data-taking period. The measurement is performed by combining the measurements of the electromagnetic calorimeter EMCal and the central tracking detectors ITS and TPC, covering a pseudorapidity range of |ηγ|<0.67 and a transverse momentum range of 7<pγT<200 GeV/c. The result extends to lower pγT and xγT=2pγT/s√ ranges, the lowest xγT of any isolated photon measurements to date, extending significantly those measured by the ATLAS and CMS experiments towards lower pγT at the same collision energy with a small overlap between the measurements. The measurement is compared with next-to-leading order perturbative QCD calculations and the results from the ATLAS and CMS experiments as well as with measurements at other collision energies. The measurement and theory prediction are in agreement with each other within the experimental and theoretical uncertainties.
Polyketide synthases (PKSs) are large megaenzymes that occur in bacteria, fungi, and plants and produce polyketides, a class of secondary metabolites. Many polyketide natural products exhibit high biological activities e.g. as antibiotics or anti-fungal compounds. The modular architecture of assembly line PKSs makes them exciting targets for engineering approaches via the exchange of whole modules or single domains. Although many engineering attempts have been pursued over the last three decades, the resulting chimeric PKSs often exhibit decreased turnover rates or diminished product yields.
In this thesis, new approaches to engineer chimeric PKSs were explored, each targeting a different aspect of the chimeric system: First the relative contribution of protein-protein and protein-substrate recognition on the turnover of chimeric PKS was assessed, revealing the importance of protein-protein interactions between the acyl carrier protein (ACP) and the ketosynthase (KS) domain in the chain translocation step. Directed evolution experiments followed to optimize the protein-protein interaction across a chimeric interface. Additionally, different junction sites for the generation of chimeric PKSs were compared, showing the ability for recombination without interfering with the chain translocation reaction, and highlighting the use of SYNZIP domains to bridge PKS modules. To optimize chimeric PKSs even further, multipoint mutagenesis of KS domains was established, with positive effects on the activity of chimeric systems.
To support engineering attempts, several structure elucidation techniques were combined with in silico modeling to characterize the architecture of a PKS module and the domain-domain interactions within it. Preliminary results show a strong conformational flexibility of the PKS module and the great potential of these techniques to define the multitude of transient interactions in PKS modules.
The authors regret that there is an error present in the units displayed in the sentence “The dissociation constant of docking domains or modules connected by docking domains was found to be KD 70–130 mM (ref. 35) and KD 1–2 mM (ref. 59), respectively.” within Section 3.1. Module–module exchanges. The corrected version of this sentence is as follows:
The dissociation constant of docking domains or modules connected by docking domains was found to be KD 70–130 μM (ref. 35) and KD 1–2 mM (ref. 59), respectively.
The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.
Covering: mid 1990s to 2018
Over the last two decades, diverse approaches have been explored to generate new polyketides by engineering polyketide synthases (PKSs). Although it has been proven possible to produce new compounds by designed PKSs, engineering strategies failed to make polyketides available via widely applicable rules and protocols. Still, organic synthetic routes have to be employed whenever new polyketides are needed for applications in medicine, agriculture, and industry. In light of the rising demand for commodity products from feedstock and for fast and cheap access to pharmaceutical compounds, the need for harnessing PKSs to produce such molecules is more urgent than ever before. In this review, we focus on a multitude of approaches to engineer modular PKSs by swapping and replacing PKS modules and domains, which we analyze in the light of recent structural and biochemical data. We conclude with an outlook on possible strategies on how to increase success rates of PKS engineering in future.
Middeke, Jan Moritz ; Metzeler, Klaus Hans ; Röllig, Christoph ; Krämer, Michael ; Eckardt, Jan-Niklas ; Stasik, Sebastian ; Greif, Philipp ; Spiekermann, Karsten ; Rothenberg-Thurley, Maja ; Krug, Utz ; Braess, Jan ; Krämer, Alwin ; Hochhaus, Andreas ; Brümmendorf, Tim Henrik ; Naumann, Ralph ; Steffen, Björn ; Einsele, Hermann ; Schaich, Markus ; Burchert, Andreas ; Neubauer, Andreas ; Görlich, Dennis ; Sauerland, Cristina ; Schäfer-Eckart, Kerstin ; Schliemann, Christoph ; Krause, Stefan W. ; Hänel, Mathias ; Frickhofen, Norbert ; Noppeney, Richard ; Kaiser, Ulrich ; Kaufmann, Martin ; Kunadt, Désirée ; Wörmann, Bernhard ; Sockel, Katja ; Bonin, von Malte ; Herold, Tobias ; Müller-Tidow, Carsten ; Platzbecker, Uwe ; Berdel, Wolfgang E. ; Serve, Hubert ; Baldus, Claudia ; Ehninger, Gerhard ; Schetelig, Johannes ; Hiddemann, Wolfgang ; Bornhäuser, Martin ; Stölzel, Friedrich ; Thiede, Christian
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
Proton pumping respiratory complex I is a major player in mitochondrial energy conversion. Yet little is known about the molecular mechanism of this large membrane protein complex. Understanding the details of ubiquinone reduction will be prerequisite for elucidating this mechanism. Based on a recently published partial structure of the bacterial enzyme, we scanned the proposed ubiquinone binding cavity of complex I by site-directed mutagenesis in the strictly aerobic yeast Yarrowia lipolytica. The observed changes in catalytic activity and inhibitor sensitivity followed a consistent pattern and allowed us to define three functionally important regions near the ubiquinone-reducing iron-sulfur cluster N2. We identified a likely entry path for the substrate ubiquinone and defined a region involved in inhibitor binding within the cavity. Finally, we were able to highlight a functionally critical structural motif in the active site that consisted of Tyr-144 in the 49-kDa subunit, surrounded by three conserved hydrophobic residues.
Engineering of assembly line polyketide synthases (PKSs) to produce novel bioactive compounds has been a goal for over twenty years. The apparent modularity of PKSs has inspired many engineering attempts in which entire modules or single domains were exchanged. In recent years, it has become evident that certain domain-domain interactions are evolutionarily optimized, and if disrupted, cause a decrease of the overall turnover rate of the chimeric PKS. In this study, we compared different types of chimeric PKSs in order to define the least invasive interface and to expand the toolbox for PKS engineering. We generated bimodular chimeric PKSs in which entire modules were exchanged, while either retaining a covalent linker between heterologous modules or introducing a non-covalent docking domain- or SYNZIP domain-mediated interface. These chimeric systems exhibited non-native domain-domain interactions during intermodular polyketide chain translocation. They were compared to otherwise equivalent bimodular PKSs in which a non-covalent interface was introduced between the condensing and processing parts of a module, resulting in non-native domain interactions during the extender unit acylation and polyketide chain elongation steps of their catalytic cycles. We show that the natural PKS docking domains can be efficiently substituted with SYNZIP domains and that the newly introduced non-covalent interface between the condensing and processing parts of a module can be harnessed for PKS engineering. Additionally, we established SYNZIP domains as a new tool for engineering PKSs by efficiently bridging non-native interfaces without perturbing PKS activity.
Modular polyketide synthases (PKSs) produce complex, bioactive secondary metabolites in assembly line-like multistep reactions. Longstanding efforts to produce novel, biologically active compounds by recombining intact modules to new modular PKSs have mostly resulted in poorly active chimeras and decreased product yields. Recent findings demonstrate that the low efficiencies of modular chimeric PKSs also result from rate limitations in the transfer of the growing polyketide chain across the non-cognate module:module interface and further processing of the non-native polyketide substrate by the ketosynthase (KS) domain. In this study, we aim at disclosing and understanding the low efficiency of chimeric modular PKSs and at establishing guidelines for modular PKSs engineering. To do so, we work with a bimodular PKS testbed and systematically vary substrate specificity, substrate identity, and domain:domain interfaces of the KS involved reactions. We observe that KS domains employed in our chimeric bimodular PKSs are bottlenecks with regards to both substrate specificity as well as interaction with the ACP. Overall, our systematic study can explain in quantitative terms why early oversimplified engineering strategies based on the plain shuffling of modules mostly failed and why more recent approaches show improved success rates. We moreover identify two mutations of the KS domain that significantly increased turnover rates in chimeric systems and interpret this finding in mechanistic detail.