Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian

Avalon, Nicole E.; Murray, Alison E.; Daligault, Hajnalka Erzsebet; Lo, Chien-Chi; Davenport, Karen Walston; Dichosa, Armand Earl Ko; Chain, Patrick Sam Guy; Baker, Bill J.

doi:10.3389/fchem.2021.802574

Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian

Journal Article · Thu Dec 23 23:00:00 EST 2021 · Frontiers in Chemistry

DOI:https://doi.org/10.3389/fchem.2021.802574· OSTI ID:1968219

Avalon, Nicole E. ^[1]; Murray, Alison E. ^[2]; ^[3]; ^[3]; ^[3]; ^[3]; ^[3]; Baker, Bill J. ^[1]

Univ. of South Florida, Tampa, FL (United States)
Desert Research Inst. (DRI), Reno, NV (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Complex interactions exist between microbiomes and their hosts. Increasingly, defensive metabolites that have been attributed to host biosynthetic capability are now being recognized as products of host-associated microbes. These unique metabolites often have bioactivity targets in human disease and can be purposed as pharmaceuticals. Polyketides are a complex family of natural products that often serve as defensive metabolites for competitive or pro-survival purposes for the producing organism, while demonstrating bioactivity in human diseases as cholesterol lowering agents, anti-infectives, and anti-tumor agents. Marine invertebrates and microbes are a rich source of polyketides. Palmerolide A, a polyketide isolated from the Antarctic ascidian Synoicum adareanum, is a vacuolar-ATPase inhibitor with potent bioactivity against melanoma cell lines. The biosynthetic gene clusters (BGCs) responsible for production of secondary metabolites are encoded in the genomes of the producers as discrete genomic elements. A candidate palmerolide BGC was identified from a S. adareanum microbiome-metagenome based on a high degree of congruence with a chemical structure-based retrobiosynthetic prediction. Protein family homology analysis, conserved domain searches, active site and motif identification were used to identify and propose the function of the ~75 kbp trans-acyltransferase (AT) polyketide synthase-non-ribosomal synthase (PKS-NRPS) domains responsible for the stepwise synthesis of palmerolide A. Though PKS systems often act in a predictable co-linear sequence, this BGC includes multiple trans-acting enzymatic domains, a non-canonical condensation termination domain, a bacterial luciferase-like monooxygenase (LLM), and is found in multiple copies within the metagenome-assembled genome (MAG). Detailed inspection of the five highly similar pal BGC copies suggests the potential for biosynthesis of other members of the palmerolide chemical family. This is the first delineation of a biosynthetic gene cluster from an Antarctic microbial species, recently proposed as Candidatus Synoicihabitans palmerolidicus. These findings have relevance for fundamental knowledge of PKS combinatorial biosynthesis and could enhance drug development efforts of palmerolide A through heterologous gene expression.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1968219

Report Number(s):: LA-UR-23-23080

Journal Information:: Frontiers in Chemistry, Journal Name: Frontiers in Chemistry Vol. 9; ISSN 2296-2646

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

References (94)

The Final Steps of Bacillaene Biosynthesis in Bacillus amyloliquefaciens FZB42: Direct Evidence for β,γ Dehydration by a trans-Acyltransferase Polyketide Synthase Moldenhauer, Jana; Götz, Daniel C. G.; Albert, Christian R. Angewandte Chemie, Vol. 122, Issue 8 https://doi.org/10.1002/ange.200905468	journal	January 2010
Biosynthesis of the Antibiotic Bacillaene, the Product of a Giant Polyketide Synthase Complex of thetrans-AT Family Moldenhauer, Jana; Chen, Xiao-Hua; Borriss, Rainer Angewandte Chemie International Edition, Vol. 46, Issue 43 https://doi.org/10.1002/anie.200703386	journal	November 2007
The Biosynthetic Logic of Polyketide Diversity Hertweck, Christian Angewandte Chemie International Edition, Vol. 48, Issue 26 https://doi.org/10.1002/anie.200806121	journal	June 2009
The Interplay between a Multifunctional Dehydratase Domain and a C-Methyltransferase Effects Olefin Shift in Ambruticin Biosynthesis Berkhan, Gesche; Merten, Christian; Holec, Claudia Angewandte Chemie International Edition, Vol. 55, Issue 43 https://doi.org/10.1002/anie.201607827	journal	September 2016
A Shimizu Non-Aldol Approach to the Formal Total Synthesis of Palmerolide A Pujari, Sandip A.; Gowrisankar, Parthasarathy; Kaliappan, Krishna P. Chemistry - An Asian Journal, Vol. 6, Issue 11 https://doi.org/10.1002/asia.201100429	journal	September 2011
Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A Erol , Özlem; Schäberle , Till F.; Schmitz, Alexander ChemBioChem, Vol. 11, Issue 9 https://doi.org/10.1002/cbic.201000085	journal	May 2010
Analysis of the Sorangicin Gene Cluster Reinforces the Utility of a Combined Phylogenetic/Retrobiosynthetic Analysis for Deciphering Natural Product Assembly by trans-AT PKS Irschik, Herbert; Kopp, Maren; Weissman, Kira J. ChemBioChem, Vol. 11, Issue 13 https://doi.org/10.1002/cbic.201000313	journal	August 2010
Functional Characterization of Different ORFs Including Luciferase-Like Monooxygenase Genes from the Mensacarcin Gene Cluster Maier, Sarah; Heitzler, Tanja; Asmus, Katharina ChemBioChem, Vol. 16, Issue 8 https://doi.org/10.1002/cbic.201500048	journal	April 2015
The Phormidolide Biosynthetic Gene Cluster: Atrans-AT PKS Pathway Encoding a Toxic Macrocyclic Polyketide Bertin, Matthew J.; Vulpanovici, Alexandra; Monroe, Emily A. ChemBioChem, Vol. 17, Issue 2 https://doi.org/10.1002/cbic.201500467	journal	December 2015
Formal Total Synthesis of Palmerolide A Pawar, Amit B.; Prasad, Kavirayani R. Chemistry - A European Journal, Vol. 18, Issue 47 https://doi.org/10.1002/chem.201202324	journal	October 2012
Thioesterases: A new perspective based on their primary and tertiary structures: Thioesterases: A New Perspective Cantu, David C.; Chen, Yingfei; Reilly, Peter J. Protein Science, Vol. 19, Issue 7 https://doi.org/10.1002/pro.417	journal	May 2010
Rotation, Structure, and Classification of Prokaryotic V-ATPase Yokoyama, Ken; Imamura, Hiromi Journal of Bioenergetics and Biomembranes, Vol. 37, Issue 6 https://doi.org/10.1007/s10863-005-9480-1	journal	December 2005
Bacterial l-leucine catabolism as a source of secondary metabolites Díaz-Pérez, Alma L.; Díaz-Pérez, César; Campos-García, Jesús Reviews in Environmental Science and Bio/Technology, Vol. 15, Issue 1 https://doi.org/10.1007/s11157-015-9385-3	journal	October 2015
Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases Haydock, Stephen F.; Aparicio, Jesús F.; Molnár, István FEBS Letters, Vol. 374, Issue 2 https://doi.org/10.1016/0014-5793(95)01119-Y	journal	October 1995
Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics Jenkins, Gail; Cundliffe, Eric Gene, Vol. 108, Issue 1 https://doi.org/10.1016/0378-1119(91)90487-V	journal	December 1991
Computational Approach for Prediction of Domain Organization and Substrate Specificity of Modular Polyketide Synthases Yadav, Gitanjali; Gokhale, Rajesh S.; Mohanty, Debasisa Journal of Molecular Biology, Vol. 328, Issue 2 https://doi.org/10.1016/S0022-2836(03)00232-8	journal	April 2003
Reconciling the many faces of lateral gene transfer Lawrence, Jeffrey G.; Ochman, Howard Trends in Microbiology, Vol. 10, Issue 1 https://doi.org/10.1016/S0966-842X(01)02282-X	journal	January 2002
Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase Wilkinson, Barrie; Foster, Graham; Rudd, Brian AM Chemistry & Biology, Vol. 7, Issue 2 https://doi.org/10.1016/S1074-5521(00)00076-4	journal	February 2000
Structure–activity relationship study on 13-deoxytedanolide, a highly antitumor macrolide from the marine sponge Mycale adhaerens Nishimura, Shinichi; Matsunaga, Shigeki; Yoshida, Satoru Bioorganic & Medicinal Chemistry, Vol. 13, Issue 2 https://doi.org/10.1016/j.bmc.2004.10.014	journal	January 2005
Palmerolide macrolides from the Antarctic tunicate Synoicum adareanum Noguez, Jaime H.; Diyabalanage, Thushara K. K.; Miyata, Yoshinari Bioorganic & Medicinal Chemistry, Vol. 19, Issue 22 https://doi.org/10.1016/j.bmc.2011.06.004	journal	November 2011
Structure and Biosynthesis of the Jamaicamides, New Mixed Polyketide-Peptide Neurotoxins from the Marine Cyanobacterium Lyngbya majuscula Edwards, Daniel J.; Marquez, Brian L.; Nogle, Lisa M. Chemistry & Biology, Vol. 11, Issue 6 https://doi.org/10.1016/j.chembiol.2004.03.030	journal	June 2004
Isolation and Purification of a New Kalimantacin/Batumin-Related Polyketide Antibiotic and Elucidation of Its Biosynthesis Gene Cluster Mattheus, Wesley; Gao, Ling-Jie; Herdewijn, Piet Chemistry & Biology, Vol. 17, Issue 2 https://doi.org/10.1016/j.chembiol.2010.01.014	journal	February 2010
Polyketide β-Branching in Bryostatin Biosynthesis: Identification of Surrogate Acetyl-ACP Donors for BryR, an HMG-ACP Synthase Buchholz, Tonia J.; Rath, Christopher M.; Lopanik, Nicole B. Chemistry & Biology, Vol. 17, Issue 10 https://doi.org/10.1016/j.chembiol.2010.08.008	journal	October 2010
Crossroads of Antibiotic Resistance and Biosynthesis Wencewicz, Timothy A. Journal of Molecular Biology, Vol. 431, Issue 18 https://doi.org/10.1016/j.jmb.2019.06.033	journal	August 2019
The Structure of a Ketoreductase Determines the Organization of the β-Carbon Processing Enzymes of Modular Polyketide Synthases Keatinge-Clay, Adrian T.; Stroud, Robert M. Structure, Vol. 14, Issue 4 https://doi.org/10.1016/j.str.2006.01.009	journal	April 2006
Synthesis of the C3–14 fragment of palmerolide A using a chiral pool based strategy Lebar, Matthew D.; Baker, Bill J. Tetrahedron, Vol. 66, Issue 8 https://doi.org/10.1016/j.tet.2009.12.007	journal	February 2010
Direct Pathway Cloning (DiPaC) to unlock natural product biosynthetic potential Greunke, Christian; Duell, Elke Regina; D’Agostino, Paul Michael Metabolic Engineering, Vol. 47 https://doi.org/10.1016/j.ymben.2018.03.010	journal	May 2018
Evolution and Diversity of Assembly-Line Polyketide Synthases: Focus Review Nivina, Aleksandra; Yuet, Kai P.; Hsu, Jake Chemical Reviews, Vol. 119, Issue 24 https://doi.org/10.1021/acs.chemrev.9b00525	journal	December 2019
Assessment of Anabaena sp. Strain PCC 7120 as a Heterologous Expression Host for Cyanobacterial Natural Products: Production of Lyngbyatoxin A Videau, Patrick; Wells, Kaitlyn N.; Singh, Arun J. ACS Synthetic Biology, Vol. 5, Issue 9 https://doi.org/10.1021/acssynbio.6b00038	journal	June 2016
Alteration of the Substrate Specificity of a Modular Polyketide Synthase Acyltransferase Domain through Site-Specific Mutations ^† Reeves, Christopher D.; Murli, Sumati; Ashley, Gary W. Biochemistry, Vol. 40, Issue 51 https://doi.org/10.1021/bi015864r	journal	December 2001
A Bidomain Nonribosomal Peptide Synthetase Encoded by FUM14 Catalyzes the Formation of Tricarballylic Esters in the Biosynthesis of Fumonisins Zaleta-Rivera, Kathia; Xu, Chunping; Yu, Fengan Biochemistry, Vol. 45, Issue 8 https://doi.org/10.1021/bi052085s	journal	February 2006
Comparative Analysis of the Substrate Specificity of trans - versus cis- Acyltransferases of Assembly Line Polyketide Synthases Dunn, Briana J.; Watts, Katharine R.; Robbins, Thomas Biochemistry, Vol. 53, Issue 23 https://doi.org/10.1021/bi5004316	journal	June 2014
Lobatamide C: Total Synthesis, Stereochemical Assignment, Preparation of Simplified Analogues, and V-ATPase Inhibition Studies Shen, Ruichao; Lin, Cheng Ting; Bowman, Emma Jean Journal of the American Chemical Society, Vol. 125, Issue 26 https://doi.org/10.1021/ja0352350	journal	June 2003
Palmerolide A, a Cytotoxic Macrolide from the Antarctic Tunicate Synoicum a dareanum Diyabalanage, Thushara; Amsler, Charles D.; McClintock, James B. Journal of the American Chemical Society, Vol. 128, Issue 17 https://doi.org/10.1021/ja0588508	journal	May 2006
Total Synthesis and Structure Revision of the Marine Metabolite Palmerolide A Jiang, Xin; Liu, Bo; Lebreton, Sylvain Journal of the American Chemical Society, Vol. 129, Issue 20 https://doi.org/10.1021/ja0715142	journal	April 2007
Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A and Isomers Thereof Nicolaou, K. C.; Sun, Ya-Ping; Guduru, Ramakrishna Journal of the American Chemical Society, Vol. 130, Issue 11 https://doi.org/10.1021/ja710485n	journal	February 2008
Chemical Synthesis and Biological Evaluation of Palmerolide A Analogues Nicolaou, K. C.; Leung, Gulice Y. C.; Dethe, Dattatraya H. Journal of the American Chemical Society, Vol. 130, Issue 30 https://doi.org/10.1021/ja802803e	journal	July 2008
Catalytic Asymmetric Synthesis of Palmerolide A via Organoboron Methodology Penner, Marlin; Rauniyar, Vivek; Kaspar, Ludwig T. Journal of the American Chemical Society, Vol. 131, Issue 40 https://doi.org/10.1021/ja906429c	journal	September 2009
Biosynthetic Pathway and Gene Cluster Analysis of Curacin A, an Antitubulin Natural Product from the Tropical Marine Cyanobacterium Lyngbya majuscula Chang, Zunxue; Sitachitta, Namthip; Rossi, James V. Journal of Natural Products, Vol. 67, Issue 8, p. 1356-1367 https://doi.org/10.1021/np0499261	journal	August 2004
Identification of the Putative Bryostatin Polyketide Synthase Gene Cluster from “ Candidatus Endobugula sertula”, the Uncultivated Microbial Symbiont of the Marine Bryozoan Bugula neritina Sudek, Sebastian; Lopanik, Nicole B.; Waggoner, Laura E. Journal of Natural Products, Vol. 70, Issue 1 https://doi.org/10.1021/np060361d	journal	December 2006
Characterization of the Microbial Community and Polyketide Biosynthetic Potential in the Palmerolide-Producing Tunicate Synoicum adareanum Riesenfeld, Christian S.; Murray, Alison E.; Baker, Bill J. Journal of Natural Products, Vol. 71, Issue 11 https://doi.org/10.1021/np800287n	journal	December 2008
Heterologous Production of 4- O -Demethylbarbamide, a Marine Cyanobacterial Natural Product Kim, Eun Ji; Lee, Jong Hyun; Choi, Hyukjae Organic Letters, Vol. 14, Issue 23 https://doi.org/10.1021/ol302575h	journal	November 2012
Formal Synthesis of Palmerolide A, Featuring Alkynogenic Fragmentation and syn-Selective Vinylogous Aldol Chemistry Lisboa, Marilda P.; Jones, David M.; Dudley, Gregory B. Organic Letters, Vol. 15, Issue 4 https://doi.org/10.1021/ol400014e	journal	February 2013
Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion Tatsuno, Satoshi; Arakawa, Kenji; Kinashi, Haruyasu The Journal of Antibiotics, Vol. 60, Issue 11 https://doi.org/10.1038/ja.2007.90	journal	November 2007
Metamorphic enzyme assembly in polyketide diversification Gu, Liangcai; Wang, Bo; Kulkarni, Amol Nature, Vol. 459, Issue 7247 https://doi.org/10.1038/nature07870	journal	June 2009
Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection Nguyen, TuAnh; Ishida, Keishi; Jenke-Kodama, Holger Nature Biotechnology, Vol. 26, Issue 2 https://doi.org/10.1038/nbt1379	journal	January 2008
Trading molecules and tracking targets in symbiotic interactions Schmidt, Eric W. Nature Chemical Biology, Vol. 4, Issue 8 https://doi.org/10.1038/nchembio.101	journal	July 2008
Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont Wakimoto, Toshiyuki; Egami, Yoko; Nakashima, Yu Nature Chemical Biology, Vol. 10, Issue 8 https://doi.org/10.1038/nchembio.1573	journal	June 2014
Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting Fisch, Katja M.; Gurgui, Cristian; Heycke, Nina Nature Chemical Biology, Vol. 5, Issue 7 https://doi.org/10.1038/nchembio.176	journal	May 2009
Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms Ueoka, Reiko; Uria, Agustinus R.; Reiter, Silke Nature Chemical Biology, Vol. 11, Issue 9 https://doi.org/10.1038/nchembio.1870	journal	August 2015
Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster matching Dejong, Chris A.; Chen, Gregory M.; Li, Haoxin Nature Chemical Biology, Vol. 12, Issue 12 https://doi.org/10.1038/nchembio.2188	journal	October 2016
Automated structure prediction of trans-acyltransferase polyketide synthase products Helfrich, Eric J. N.; Ueoka, Reiko; Dolev, Alon Nature Chemical Biology, Vol. 15, Issue 8 https://doi.org/10.1038/s41589-019-0313-7	journal	July 2019
Polyketide stereotetrads in natural products Koskinen, Ari M. P.; Karisalmi, Kaisa Chemical Society Reviews, Vol. 34, Issue 8 https://doi.org/10.1039/b417466f	journal	January 2005
Visualizing the spatial distribution of secondary metabolites produced by marine cyanobacteria and sponges via MALDI-TOF imaging Esquenazi, Eduardo; Coates, Cameron; Simmons, Luke Molecular BioSystems, Vol. 4, Issue 6 https://doi.org/10.1039/b720018h	journal	January 2008
The structures of type I polyketide synthases Keatinge-Clay, Adrian T. Natural Product Reports, Vol. 29, Issue 10 https://doi.org/10.1039/c2np20019h	journal	January 2012
Biosynthesis of polyketides by trans-AT polyketide synthases Helfrich, Eric J. N.; Piel, Jörn Natural Product Reports, Vol. 33, Issue 2 https://doi.org/10.1039/c5np00125k	journal	January 2016
Marine natural products Carroll, Anthony R.; Copp, Brent R.; Davis, Rohan A. Natural Product Reports, Vol. 36, Issue 1 https://doi.org/10.1039/c8np00092a	journal	January 2019
Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus Quiros, Luis M.; Aguirrezabalaga, Ignacio; Olano, Carlos Molecular Microbiology, Vol. 28, Issue 6 https://doi.org/10.1046/j.1365-2958.1998.00880.x	journal	June 1998
Synthetic Studies on a Marine Natural Product, Palmerolide A: Synthesis of C1-C9 and C15-C21 Fragments Kaliappan, Krishna; Gowrisankar, Parthasarathy Synlett, Vol. 2007, Issue 10 https://doi.org/10.1055/s-2007-982539	journal	June 2007
Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei Piel, J.; Hui, D.; Wen, G. Proceedings of the National Academy of Sciences, Vol. 101, Issue 46 https://doi.org/10.1073/pnas.0405976101	journal	November 2004
Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation Bordeleau, Marie-Eve; Matthews, James; Wojnar, Joanna M. Proceedings of the National Academy of Sciences, Vol. 102, Issue 30 https://doi.org/10.1073/pnas.0504249102	journal	July 2005
Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis Cheng, Y. -Q.; Tang, G. -L.; Shen, B. Proceedings of the National Academy of Sciences, Vol. 100, Issue 6 https://doi.org/10.1073/pnas.0537286100	journal	February 2003
A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis Lin, Shuangjun; Van Lanen, Steven G.; Shen, Ben Proceedings of the National Academy of Sciences, Vol. 106, Issue 11 https://doi.org/10.1073/pnas.0808880106	journal	March 2009
Insights into the lifestyle of uncultured bacterial natural product factories associated with marine sponges Lackner, Gerald; Peters, Eike Edzard; Helfrich, Eric J. N. Proceedings of the National Academy of Sciences, Vol. 114, Issue 3 https://doi.org/10.1073/pnas.1616234114	journal	January 2017
Unraveling the iterative type I polyketide synthases hidden in Streptomyces Wang, Bin; Guo, Fang; Huang, Chunshuai Proceedings of the National Academy of Sciences, Vol. 117, Issue 15 https://doi.org/10.1073/pnas.1917664117	journal	March 2020
A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles Piel, J. Proceedings of the National Academy of Sciences, Vol. 99, Issue 22 https://doi.org/10.1073/pnas.222481399	journal	October 2002
Peptide Bond Formation in Nonribosomal Peptide Biosynthesis: CATALYTIC ROLE OF THE CONDENSATION DOMAIN Stachelhaus, Torsten; Mootz, Henning D.; Bergendahl, Veit Journal of Biological Chemistry, Vol. 273, Issue 35 https://doi.org/10.1074/jbc.273.35.22773	journal	August 1998
Oxazolomycin Biosynthesis in Streptomyces albus JA3453 Featuring an “Acyltransferase-less” Type I Polyketide Synthase That Incorporates Two Distinct Extender Units Zhao, Chunhua; Coughlin, Jane M.; Ju, Jianhua Journal of Biological Chemistry, Vol. 285, Issue 26 https://doi.org/10.1074/jbc.M109.090092	journal	April 2010
Terminal Alkene Formation by the Thioesterase of Curacin A Biosynthesis: STRUCTURE OF A DECARBOXYLATING THIOESTERASE Gehret, Jennifer J.; Gu, Liangcai; Gerwick, William H. Journal of Biological Chemistry, Vol. 286, Issue 16 https://doi.org/10.1074/jbc.M110.214635	journal	February 2011
Bacterial Biosynthetic Gene Clusters Encoding the Anti-cancer Haterumalide Class of Molecules Matilla, Miguel A.; Stöckmann, Henning; Leeper, Finian J. Journal of Biological Chemistry, Vol. 287, Issue 46 https://doi.org/10.1074/jbc.M112.401026	journal	November 2012
Mode of Cell Death Induction by Pharmacological Vacuolar H+-ATPase (V-ATPase) Inhibition von Schwarzenberg, Karin; Wiedmann, Romina M.; Oak, Prajakta Journal of Biological Chemistry, Vol. 288, Issue 2 https://doi.org/10.1074/jbc.M112.412007	journal	January 2013
Identification of a New Chondropsin Class of Antitumor Compound That Selectively Inhibits V-ATPases Bowman, Emma Jean; Gustafson, Kirk R.; Bowman, Barry J. Journal of Biological Chemistry, Vol. 278, Issue 45 https://doi.org/10.1074/jbc.M306595200	journal	November 2003
Characterization of the Polyoxin Biosynthetic Gene Cluster from Streptomyces cacaoi and Engineered Production of Polyoxin H Chen, Wenqing; Huang, Tingting; He, Xinyi Journal of Biological Chemistry, Vol. 284, Issue 16 https://doi.org/10.1074/jbc.M807534200	journal	April 2009
Ecology of Antarctic Marine Sponges: An Overview McClintock, J. B. Integrative and Comparative Biology, Vol. 45, Issue 2 https://doi.org/10.1093/icb/45.2.359	journal	April 2005
Evolutionary Implications of Bacterial Polyketide Synthases Jenke-Kodama, Holger; Sandmann, Axel; Müller, Rolf Molecular Biology and Evolution, Vol. 22, Issue 10 https://doi.org/10.1093/molbev/msi193	journal	June 2005
NRPSpredictor2—a web server for predicting NRPS adenylation domain specificity Röttig, Marc; Medema, Marnix H.; Blin, Kai Nucleic Acids Research, Vol. 39, Issue suppl_2 https://doi.org/10.1093/nar/gkr323	journal	May 2011
antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline Blin, Kai; Shaw, Simon; Steinke, Katharina Nucleic Acids Research, Vol. 47, Issue W1 https://doi.org/10.1093/nar/gkz310	journal	April 2019
MIBiG 2.0: a repository for biosynthetic gene clusters of known function Kautsar, Satria A.; Blin, Kai; Shaw, Simon Nucleic Acids Research https://doi.org/10.1093/nar/gkz882	journal	October 2019
Evolutionary dynamics at high latitudes: speciation and extinction in polar marine faunas Clarke, Andrew; Crame, J. Alistair Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 365, Issue 1558 https://doi.org/10.1098/rstb.2010.0270	journal	November 2010
Quorum-sensing-dependent regulation of biosynthesis of the polyketide antibiotic mupirocin in Pseudomonas fluorescens NCIMB 10586 The GenBank accession numbers for the sequences determined in this work are AF318063 (mupA), AF318064 (mupR) and AF318065 (mupI). El-Sayed, A. Kassem; Hothersall, Joanne; Thomas, Christopher M. Microbiology, Vol. 147, Issue 8 https://doi.org/10.1099/00221287-147-8-2127	journal	August 2001
Organization of the biosynthetic gene cluster for the macrolide concanamycin A in Streptomyces neyagawaensis ATCC 27449 Haydock, Stephen F.; Appleyard, Anthony N.; Mironenko, Tatiana Microbiology, Vol. 151, Issue 10 https://doi.org/10.1099/mic.0.28194-0	journal	October 2005
The secret to a successful relationship: lasting chemistry between ascidians and their symbiotic bacteria Schmidt, Eric W. Invertebrate Biology, Vol. 134, Issue 1 https://doi.org/10.1111/ivb.12071	journal	October 2014
Characterization of a Glycosyl Transferase Inactivating Macrolides, Encoded by gimA from Streptomyces ambofaciens Gourmelen, Anne; Blondelet-Rouault, Marie-Hélène; Pernodet, Jean-Luc Antimicrobial Agents and Chemotherapy, Vol. 42, Issue 10 https://doi.org/10.1128/aac.42.10.2612	journal	October 1998
Discovery of an Antarctic Ascidian-Associated Uncultivated Verrucomicrobia with Antimelanoma Palmerolide Biosynthetic Potential Murray, Alison E.; Lo, Chien-Chi; Daligault, Hajnalka E. mSphere, Vol. 6, Issue 6 https://doi.org/10.1128/mSphere.00759-21	journal	December 2021
Increased Biosynthetic Gene Dosage in a Genome-Reduced Defensive Bacterial Symbiont Lopera, Juan; Miller, Ian J.; McPhail, Kerry L. mSystems, Vol. 2, Issue 6 https://doi.org/10.1128/mSystems.00096-17	journal	November 2017
Structure and Mechanism of the 6-Deoxyerythronolide B Synthase Khosla, Chaitan; Tang, Yinyan; Chen, Alice Y. Annual Review of Biochemistry, Vol. 76, Issue 1 https://doi.org/10.1146/annurev.biochem.76.053105.093515	journal	June 2007
Iejimalides Show Anti-Osteoclast ActivityviaV-ATPase Inhibition Kazami, Sayaka; Muroi, Makoto; Kawatani, Makoto Bioscience, Biotechnology, and Biochemistry, Vol. 70, Issue 6 https://doi.org/10.1271/bbb.50644	journal	June 2006
Inferring Horizontal Gene Transfer Ravenhall, Matt; Škunca, Nives; Lassalle, Florent PLOS Computational Biology, Vol. 11, Issue 5 https://doi.org/10.1371/journal.pcbi.1004095	journal	May 2015
Ancient Horizontal Gene Transfer from Bacteria Enhances Biosynthetic Capabilities of Fungi Schmitt, Imke; Lumbsch, H. Thorsten PLoS ONE, Vol. 4, Issue 2 https://doi.org/10.1371/journal.pone.0004437	journal	February 2009
A Putative Gene Cluster from a Lyngbya wollei Bloom that Encodes Paralytic Shellfish Toxin Biosynthesis Mihali, Troco K.; Carmichael, Wayne W.; Neilan, Brett A. PLoS ONE, Vol. 6, Issue 2 https://doi.org/10.1371/journal.pone.0014657	journal	February 2011
Genomic and Metabolomic Insights into the Natural Product Biosynthetic Diversity of a Feral-Hog-Associated Brevibacillus laterosporus Strain Theodore, Christine M.; Stamps, Blake W.; King, Jarrod B. PLoS ONE, Vol. 9, Issue 3 https://doi.org/10.1371/journal.pone.0090124	journal	March 2014
Marine Macrolides, a Promising Source of Antitumor Compounds Napolitano, Jose G.; Daranas, Antonio H.; Norte, Manuel Anti-Cancer Agents in Medicinal Chemistry, Vol. 9, Issue 2 https://doi.org/10.2174/187152009787313800	journal	February 2009
Site-Specific Variability in the Chemical Diversity of the Antarctic Red Alga Plocamium cartilagineum Young, Ryan; von Salm, Jacqueline; Amsler, Margaret Marine Drugs, Vol. 11, Issue 6 https://doi.org/10.3390/md11062126	journal	June 2013
Uncovering the Core Microbiome and Distribution of Palmerolide in Synoicum adareanum Across the Anvers Island Archipelago, Antarctica Murray, Alison E.; Avalon, Nicole E.; Bishop, Lucas Marine Drugs, Vol. 18, Issue 6 https://doi.org/10.3390/md18060298	journal	June 2020

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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