Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

Daruwalla, Anahita; Zhang, Jianye; Lee, Ho Jun; Khadka, Nimesh; Farquhar, Erik R.; Shi, Wuxian; von Lintig, Johannes; Kiser, Philip D.

doi:10.1073/pnas.2004116117

Title: Structural basis for carotenoid cleavage by an archaeal carotenoid dioxygenase

Journal Article · Tue Aug 18 00:00:00 EDT 2020 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2004116117· OSTI ID:1668655

^[1]; Zhang, Jianye ^[2];

^[2]; Khadka, Nimesh ^[3];

^[4]; Shi, Wuxian ^[5];

^[3];

^[6]

Univ. of California School of Medicine, Irvine, CA (United States); Case Western Reserve Univ. of Medicine, Cleveland, OH (United States)
Univ. of California School of Medicine, Irvine, CA (United States)
Case Western Reserve Univ. of Medicine, Cleveland, OH (United States)
Case Western Reserve Univ. of Medicine, Cleveland, OH (United States); Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
Univ. of California School of Medicine, Irvine, CA (United States); Veterans Affairs Long Beach Healthcare System, Long Beach, CA (United States)

Apocarotenoids are important signaling molecules generated from carotenoids through the action of carotenoid cleavage dioxygenases (CCDs). These enzymes have a remarkable ability to cleave carotenoids at specific alkene bonds while leaving chemically similar sites within the polyene intact. Although several bacterial and eukaryotic CCDs have been characterized, the long-standing goal of experimentally visualizing a CCD–carotenoid complex at high resolution to explain this exquisite regioselectivity remains unfulfilled. CCD genes are also present in some archaeal genomes, but the encoded enzymes remain uninvestigated. Here, we address this knowledge gap through analysis of a metazoan-like archaeal CCD from Candidatus Nitrosotalea devanaterra (NdCCD). Nd CCD was active toward β-apocarotenoids but did not cleave bicyclic carotenoids. It exhibited an unusual regiospecificity, cleaving apocarotenoids solely at the C14'–C13' alkene bond to produce β-apo-14'-carotenals. The structure of Nd CCD revealed a tapered active site cavity markedly different from the broad active site observed for the retinal-forming Synechocystis apocarotenoid oxygenase ( Syn ACO) but similar to the vertebrate retinoid isomerase RPE65. The structure of Nd CCD in complex with its apocarotenoid product demonstrated that the site of cleavage is defined by interactions along the substrate binding cleft as well as selective stabilization of reaction intermediates at the scissile alkene. These data on the molecular basis of CCD catalysis shed light on the origins of the varied catalytic activities found in metazoan CCDs, opening the possibility of modifying their activity through rational chemical or genetic approaches.

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Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC0012704

OSTI ID:: 1668655

Report Number(s):: BNL-219888-2020-JAAM

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, Issue 33; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (62)

Identification of a Novel Palmitylation Site Essential for Membrane Association and Isomerohydrolase Activity of RPE65 Takahashi, Yusuke; Moiseyev, Gennadiy; Ablonczy, Zsolt Journal of Biological Chemistry, Vol. 284, Issue 5 https://doi.org/10.1074/jbc.M807248200	journal	December 2008
Archaea: Essential inhabitants of the human digestive microbiota Nkamga, Vanessa Demonfort; Henrissat, Bernard; Drancourt, Michel Human Microbiome Journal, Vol. 3 https://doi.org/10.1016/j.humic.2016.11.005	journal	March 2017
Asgard archaea illuminate the origin of eukaryotic cellular complexity Zaremba-Niedzwiedzka, Katarzyna; Caceres, Eva F.; Saw, Jimmy H. Nature, Vol. 541, Issue 7637 https://doi.org/10.1038/nature21031	journal	January 2017
Electrostatics of nanosystems: Application to microtubules and the ribosome Baker, N. A.; Sept, D.; Joseph, S. Proceedings of the National Academy of Sciences, Vol. 98, Issue 18, p. 10037-10041 https://doi.org/10.1073/pnas.181342398	journal	August 2001
Phylogenomics provides robust support for a two-domains tree of life Williams, Tom A.; Cox, Cymon J.; Foster, Peter G. Nature Ecology & Evolution, Vol. 4, Issue 1 https://doi.org/10.1038/s41559-019-1040-x	journal	December 2019
Electric Fields and Enzyme Catalysis Fried, Stephen D.; Boxer, Steven G. Annual Review of Biochemistry, Vol. 86, Issue 1 https://doi.org/10.1146/annurev-biochem-061516-044432	journal	June 2017
Bacterial gene import and mesophilic adaptation in archaea López-García, Purificación; Zivanovic, Yvan; Deschamps, Philippe Nature Reviews Microbiology, Vol. 13, Issue 7 https://doi.org/10.1038/nrmicro3485	journal	June 2015
Carotene Oxygenases: A New Family of Double Bond Cleavage Enzymes Wyss, Adrian The Journal of Nutrition, Vol. 134, Issue 1 https://doi.org/10.1093/jn/134.1.246S	journal	January 2004
Phylogenetic analysis of the metazoan carotenoid oxygenase superfamily: a new ancestral gene assemblage of BCO-like (BCOL) proteins Poliakov, Eugenia; Soucy, Joseph; Gentleman, Susan Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-13521-x	journal	October 2017
A mitochondrial enzyme degrades carotenoids and protects against oxidative stress Amengual, Jaume; Lobo, Glenn P.; Golczak, Marcin The FASEB Journal, Vol. 25, Issue 3 https://doi.org/10.1096/fj.10-173906	journal	November 2010
Apocarotenoids: Emerging Roles in Mammals Harrison, Earl H.; Quadro, Loredana Annual Review of Nutrition, Vol. 38, Issue 1 https://doi.org/10.1146/annurev-nutr-082117-051841	journal	August 2018
Biochemical evidence for the tyrosine involvement in cationic intermediate stabilization in mouse β-carotene 15, 15'-monooxygenase Poliakov, Eugenia; Gentleman, Susan; Chander, Preethi BMC Biochemistry, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2091-10-31	journal	December 2009
Origin of eukaryotes from within archaea, archaeal eukaryome and bursts of gene gain: eukaryogenesis just made easier? Koonin, Eugene V. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 370, Issue 1678 https://doi.org/10.1098/rstb.2014.0333	journal	September 2015
The Biochemical Basis of Vitamin A Production from the Asymmetric Carotenoid β-Cryptoxanthin Kelly, Mary E.; Ramkumar, Srinivasagan; Sun, Weizhong ACS Chemical Biology, Vol. 13, Issue 8 https://doi.org/10.1021/acschembio.8b00290	journal	June 2018
Structural Insights into Maize Viviparous14, a Key Enzyme in the Biosynthesis of the Phytohormone Abscisic Acid Messing, Simon A. J.; Gabelli, Sandra B.; Echeverria, Ignacia The Plant Cell, Vol. 22, Issue 9 https://doi.org/10.1105/tpc.110.074815	journal	September 2010
Structure and Spectroscopy of Alkene-Cleaving Dioxygenases Containing an Atypically Coordinated Non-Heme Iron Center Sui, Xuewu; Weitz, Andrew C.; Farquhar, Erik R. Biochemistry, Vol. 56, Issue 22 https://doi.org/10.1021/acs.biochem.7b00251	journal	May 2017
Integrative modeling of gene and genome evolution roots the archaeal tree of life Williams, Tom A.; Szöllősi, Gergely J.; Spang, Anja Proceedings of the National Academy of Sciences, Vol. 114, Issue 23 https://doi.org/10.1073/pnas.1618463114	journal	May 2017
Origin and Evolution of Retinoid Isomerization Machinery in Vertebrate Visual Cycle: Hint from Jawless Vertebrates Poliakov, Eugenia; Gubin, Alexander N.; Stearn, Olivia PLoS ONE, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pone.0049975	journal	November 2012
The Mycobacterium tuberculosis ORF Rv0654 encodes a carotenoid oxygenase mediating central and excentric cleavage of conventional and aromatic carotenoids: A novel carotenoid oxygenase from M. tuberculosis Scherzinger, Daniel; Scheffer, Erdmann; Bär, Cornelia FEBS Journal, Vol. 277, Issue 22 https://doi.org/10.1111/j.1742-4658.2010.07873.x	journal	October 2010
Molecular Analysis of Vitamin A Formation: Cloning and Characterization of β-Carotene 15,15′-Dioxygenases von Lintig, Johannes; Wyss, Adrian Archives of Biochemistry and Biophysics, Vol. 385, Issue 1 https://doi.org/10.1006/abbi.2000.2096	journal	January 2001
Carotenoid oxygenases: cleave it or leave it Giuliano, Giovanni; Al-Babili, Salim; von Lintig, Johannes Trends in Plant Science, Vol. 8, Issue 4 https://doi.org/10.1016/S1360-1385(03)00053-0	journal	April 2003
Retinoic Acid and Immune Homeostasis: A Balancing Act Erkelens, Martje N.; Mebius, Reina E. Trends in Immunology, Vol. 38, Issue 3 https://doi.org/10.1016/j.it.2016.12.006	journal	March 2017
Characterization of .beta.-apo-13-carotenone and .beta.-apo-14'-carotenal as enzymic products of the excentric cleavage of .beta.-carotene Tang, Guangwen; Wang, Xiang Dong; Russell, Robert M. Biochemistry, Vol. 30, Issue 41 https://doi.org/10.1021/bi00105a003	journal	October 1991
Identification and Characterization of a Mammalian Enzyme Catalyzing the Asymmetric Oxidative Cleavage of Provitamin A Kiefer, Cornelia; Hessel, Susanne; Lampert, Johanna M. Journal of Biological Chemistry, Vol. 276, Issue 17 https://doi.org/10.1074/jbc.M011510200	journal	January 2001
Cultivation of an obligate acidophilic ammonia oxidizer from a nitrifying acid soil Lehtovirta-Morley, L. E.; Stoecker, K.; Vilcinskas, A. Proceedings of the National Academy of Sciences, Vol. 108, Issue 38 https://doi.org/10.1073/pnas.1107196108	journal	September 2011
Evolution of the Genetic Machinery of the Visual Cycle: A Novelty of the Vertebrate Eye? Albalat, R. Molecular Biology and Evolution, Vol. 29, Issue 5 https://doi.org/10.1093/molbev/msr313	journal	December 2011
Crystal structure of native RPE65, the retinoid isomerase of the visual cycle Kiser, P. D.; Golczak, M.; Lodowski, D. T. Proceedings of the National Academy of Sciences, Vol. 106, Issue 41 https://doi.org/10.1073/pnas.0906600106	journal	October 2009
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Naturally Occurring Eccentric Cleavage Products of Provitamin A β-Carotene Function as Antagonists of Retinoic Acid Receptors Eroglu, Abdulkerim; Hruszkewycz, Damian P.; dela Sena, Carlo Journal of Biological Chemistry, Vol. 287, Issue 19 https://doi.org/10.1074/jbc.M111.325142	journal	March 2012
Utilization of Dioxygen by Carotenoid Cleavage Oxygenases Sui, Xuewu; Golczak, Marcin; Zhang, Jianye Journal of Biological Chemistry, Vol. 290, Issue 51 https://doi.org/10.1074/jbc.M115.696799	journal	October 2015
Key Residues for Catalytic Function and Metal Coordination in a Carotenoid Cleavage Dioxygenase Sui, Xuewu; Zhang, Jianye; Golczak, Marcin Journal of Biological Chemistry, Vol. 291, Issue 37 https://doi.org/10.1074/jbc.M116.744912	journal	July 2016
Analysis of the blind Drosophila mutant ninaB identifies the gene encoding the key enzyme for vitamin A formation in vivo von Lintig, J.; Dreher, A.; Kiefer, C. Proceedings of the National Academy of Sciences, Vol. 98, Issue 3 https://doi.org/10.1073/pnas.98.3.1130	journal	January 2001
Editorial Fenton, André A.; Muller, Robert U. Methods, Vol. 21, Issue 4 https://doi.org/10.1006/meth.2000.1020	journal	August 2000
Structure and properties of carotenoids in relation to function. Britton, G. The FASEB Journal, Vol. 9, Issue 15 https://doi.org/10.1096/fasebj.9.15.8529834	journal	December 1995
The Structure of a Retinal-Forming Carotenoid Oxygenase Kloer, D. P. Science, Vol. 308, Issue 5719 https://doi.org/10.1126/science.1108965	journal	April 2005
Catalytic mechanism of a retinoid isomerase essential for vertebrate vision Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen Nature Chemical Biology, Vol. 11, Issue 6 https://doi.org/10.1038/nchembio.1799	journal	April 2015
In vivo and in vitro studies on the carotenoid cleavage oxygenases from Sphingopyxis alaskensis RB2256 and Plesiocystis pacifica SIR-1 revealed their substrate specificities and non-retinal-forming cleavage activities Hoffmann, Jana; Bóna-Lovász, Judit; Beuttler, Holger FEBS Journal, Vol. 279, Issue 20 https://doi.org/10.1111/j.1742-4658.2012.08751.x	journal	September 2012
Analysis of Carotenoid Isomerase Activity in a Prototypical Carotenoid Cleavage Enzyme, Apocarotenoid Oxygenase (ACO) Sui, Xuewu; Kiser, Philip D.; Che, Tao Journal of Biological Chemistry, Vol. 289, Issue 18 https://doi.org/10.1074/jbc.M114.552836	journal	March 2014
Carotenoid metabolism in mammals, including man: formation, occurrence, and function of apocarotenoids: Thematic Review Series: Fat-Soluble Vitamins: Vitamin A Eroglu, Abdulkerim; Harrison, Earl H. Journal of Lipid Research, Vol. 54, Issue 7 https://doi.org/10.1194/jlr.R039537	journal	May 2013
Palmitoylation of Metazoan Carotenoid Oxygenases Uppal, Sheetal; Rogozin, Igor B.; Redmond, T. Michael Molecules, Vol. 25, Issue 8 https://doi.org/10.3390/molecules25081942	journal	April 2020
Substrate Specificity of Purified Recombinant Chicken β-Carotene 9′,10′-Oxygenase (BCO2) dela Seña, Carlo; Sun, Jian; Narayanasamy, Sureshbabu Journal of Biological Chemistry, Vol. 291, Issue 28 https://doi.org/10.1074/jbc.M116.723684	journal	May 2016
Preparation and characterization of metal-substituted carotenoid cleavage oxygenases Sui, Xuewu; Farquhar, Erik R.; Hill, Hannah E. JBIC Journal of Biological Inorganic Chemistry, Vol. 23, Issue 6 https://doi.org/10.1007/s00775-018-1586-0	journal	June 2018
Specific Oxidative Cleavage of Carotenoids by VP14 of Maize Schwartz, S. H. Science, Vol. 276, Issue 5320 https://doi.org/10.1126/science.276.5320.1872	journal	June 1997
New Insight into the Cleavage Reaction of Nostoc sp. Strain PCC 7120 Carotenoid Cleavage Dioxygenase in Natural and Nonnatural Carotenoids Heo, Jinsol; Kim, Se Hyeuk; Lee, Pyung Cheon Applied and Environmental Microbiology, Vol. 79, Issue 11 https://doi.org/10.1128/AEM.00071-13	journal	March 2013
Archaea and the origin of eukaryotes Eme, Laura; Spang, Anja; Lombard, Jonathan Nature Reviews Microbiology, Vol. 15, Issue 12 https://doi.org/10.1038/nrmicro.2017.133	journal	November 2017
Cloning and Expression of β,β-Carotene 15,15′-Dioxygenase Wyss, A.; Wirtz, G.; Woggon, W. -D. Biochemical and Biophysical Research Communications, Vol. 271, Issue 2 https://doi.org/10.1006/bbrc.2000.2619	journal	May 2000
A Multiplet Analysis of Fe K-Edge 1s → 3d Pre-Edge Features of Iron Complexes Westre, Tami E.; Kennepohl, Pierre; DeWitt, Jane G. Journal of the American Chemical Society, Vol. 119, Issue 27 https://doi.org/10.1021/ja964352a	journal	July 1997
Plant carotenoid cleavage oxygenases and their apocarotenoid products Auldridge, Michele E.; McCarty, Donald R.; Klee, Harry J. Current Opinion in Plant Biology, Vol. 9, Issue 3 https://doi.org/10.1016/j.pbi.2006.03.005	journal	June 2006
Aromatic Residues in the Substrate Cleft of RPE65 Protein Govern Retinol Isomerization and Modulate Its Progression Chander, Preethi; Gentleman, Susan; Poliakov, Eugenia Journal of Biological Chemistry, Vol. 287, Issue 36 https://doi.org/10.1074/jbc.M112.364596	journal	June 2012
Asymmetric Cleavage of β-Carotene Yields a Transcriptional Repressor of Retinoid X Receptor and Peroxisome Proliferator-Activated Receptor Responses Ziouzenkova, Ouliana; Orasanu, Gabriela; Sukhova, Galina Molecular Endocrinology, Vol. 21, Issue 1 https://doi.org/10.1210/me.2006-0225	journal	January 2007
Structure and mechanism of NOV1, a resveratrol-cleaving dioxygenase McAndrew, Ryan P.; Sathitsuksanoh, Noppadon; Mbughuni, Michael M. Proceedings of the National Academy of Sciences, Vol. 113, Issue 50 https://doi.org/10.1073/pnas.1608917113	journal	November 2016
Retinylidene Proteins: Structures and Functions from Archaea to Humans Spudich, John L.; Yang, Chii-Shen; Jung, Kwang-Hwan Annual Review of Cell and Developmental Biology, Vol. 16, Issue 1 https://doi.org/10.1146/annurev.cellbio.16.1.365	journal	November 2000
Structural basis of carotenoid cleavage: From bacteria to mammals Sui, Xuewu; Kiser, Philip D.; Lintig, Johannes von Archives of Biochemistry and Biophysics, Vol. 539, Issue 2 https://doi.org/10.1016/j.abb.2013.06.012	journal	November 2013
Bacterioopsin-Mediated Regulation of Bacterioruberin Biosynthesis in Halobacterium salinarum Dummer, A. M.; Bonsall, J. C.; Cihla, J. B. Journal of Bacteriology, Vol. 193, Issue 20 https://doi.org/10.1128/JB.05376-11	journal	August 2011
MrBayes 3: Bayesian phylogenetic inference under mixed models Ronquist, Fredrik; Huelsenbeck, John P. Bioinformatics, Vol. 19, Issue 12, p. 1572-1574 https://doi.org/10.1093/bioinformatics/btg180	journal	August 2003
Reaction Mechanism of Apocarotenoid Oxygenase (ACO): A DFT Study Borowski, Tomasz; Blomberg, Margareta R. A.; Siegbahn, Per E. M. Chemistry - A European Journal, Vol. 14, Issue 7 https://doi.org/10.1002/chem.200701344	journal	February 2008
Using SAD data in Phaser Read, Randy J.; McCoy, Airlie J. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910051371	journal	March 2011
Structure of RPE65 isomerase in a lipidic matrix reveals roles for phospholipids and iron in catalysis Kiser, P. D.; Farquhar, E. R.; Shi, W. Proceedings of the National Academy of Sciences, Vol. 109, Issue 41 https://doi.org/10.1073/pnas.1212025109	journal	September 2012
Mechanical insights into the oxidative cleavage of resveratrol catalyzed by dioxygenase NOV1 from Novosphingobium aromaticivorans : confirmation of dioxygenase mechanism by QM/MM calculations Bai, Jie; Hou, Qianqian; Zhu, Wenyou Catalysis Science & Technology, Vol. 9, Issue 2 https://doi.org/10.1039/C8CY01885E	journal	January 2019
Structural and mechanistic aspects of carotenoid cleavage dioxygenases (CCDs) Daruwalla, Anahita; Kiser, Philip D. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1865, Issue 11 https://doi.org/10.1016/j.bbalip.2019.158590	journal	November 2020
Retina, Retinol, Retinal and the Natural History of Vitamin A as a Light Sensor Zhong, Ming; Kawaguchi, Riki; Kassai, Miki Nutrients, Vol. 4, Issue 12 https://doi.org/10.3390/nu4122069	journal	December 2012
Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro Hamel, C. P.; Tsilou, E.; Pfeffer, B. A. Journal of Biological Chemistry, Vol. 268, Issue 21 https://doi.org/10.1016/S0021-9258(18)82319-5	journal	July 1993

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