Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian
Abstract
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. Thoughmore »
- Authors:
-
[3];
[3];
[3];
[3];
[3];
- 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)
- Publication Date:
- Research Org.:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH); National Science Foundation (NSF)
- OSTI Identifier:
- 1968219
- Report Number(s):
- LA-UR-23-23080
Journal ID: ISSN 2296-2646
- Grant/Contract Number:
- 89233218CNA000001; CA205932; ANT-0838776; PLR-1341339; ANT-0632389
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Frontiers in Chemistry
- Additional Journal Information:
- Journal Volume: 9; Journal ID: ISSN 2296-2646
- Publisher:
- Frontiers Research Foundation
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; biological sciences; marine natural products; macrolide; biosynthetic gene clusters; Antarctic microbiology; trans-AT type I polyketide synthase; secondary metabolites
Citation Formats
Avalon, Nicole E., Murray, Alison E., Daligault, Hajnalka Erzsebet, Lo, Chien-Chi, Davenport, Karen Walston, Dichosa, Armand Earl Ko, Chain, Patrick Sam Guy, and Baker, Bill J. Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian. United States: N. p., 2021.
Web. doi:10.3389/fchem.2021.802574.
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. Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian. United States. https://doi.org/10.3389/fchem.2021.802574
Avalon, Nicole E., Murray, Alison E., Daligault, Hajnalka Erzsebet, Lo, Chien-Chi, Davenport, Karen Walston, Dichosa, Armand Earl Ko, Chain, Patrick Sam Guy, and Baker, Bill J. Fri .
"Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian". United States. https://doi.org/10.3389/fchem.2021.802574. https://www.osti.gov/servlets/purl/1968219.
@article{osti_1968219,
title = {Bioinformatic and Mechanistic Analysis of the Palmerolide PKS-NRPS Biosynthetic Pathway From the Microbiome of an Antarctic Ascidian},
author = {Avalon, Nicole E. and Murray, Alison E. and Daligault, Hajnalka Erzsebet and Lo, Chien-Chi and Davenport, Karen Walston and Dichosa, Armand Earl Ko and Chain, Patrick Sam Guy and Baker, Bill J.},
abstractNote = {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.},
doi = {10.3389/fchem.2021.802574},
journal = {Frontiers in Chemistry},
number = ,
volume = 9,
place = {United States},
year = {Fri Dec 24 00:00:00 EST 2021},
month = {Fri Dec 24 00:00:00 EST 2021}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster matching
journal, October 2016
- Dejong, Chris A.; Chen, Gregory M.; Li, Haoxin
- Nature Chemical Biology, Vol. 12, Issue 12
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).
journal, August 2001
- El-Sayed, A. Kassem; Hothersall, Joanne; Thomas, Christopher M.
- Microbiology, Vol. 147, Issue 8
A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles
journal, October 2002
- Piel, J.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 22
Trading molecules and tracking targets in symbiotic interactions
journal, July 2008
- Schmidt, Eric W.
- Nature Chemical Biology, Vol. 4, Issue 8
Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase
journal, February 2000
- Wilkinson, Barrie; Foster, Graham; Rudd, Brian AM
- Chemistry & Biology, Vol. 7, Issue 2
Catalytic Asymmetric Synthesis of Palmerolide A via Organoboron Methodology
journal, September 2009
- Penner, Marlin; Rauniyar, Vivek; Kaspar, Ludwig T.
- Journal of the American Chemical Society, Vol. 131, Issue 40
Visualizing the spatial distribution of secondary metabolites produced by marine cyanobacteria and sponges via MALDI-TOF imaging
journal, January 2008
- Esquenazi, Eduardo; Coates, Cameron; Simmons, Luke
- Molecular BioSystems, Vol. 4, Issue 6
Stimulation of mammalian translation initiation factor eIF4A activity by a small molecule inhibitor of eukaryotic translation
journal, July 2005
- Bordeleau, Marie-Eve; Matthews, James; Wojnar, Joanna M.
- Proceedings of the National Academy of Sciences, Vol. 102, Issue 30
Terminal Alkene Formation by the Thioesterase of Curacin A Biosynthesis: STRUCTURE OF A DECARBOXYLATING THIOESTERASE
journal, February 2011
- Gehret, Jennifer J.; Gu, Liangcai; Gerwick, William H.
- Journal of Biological Chemistry, Vol. 286, Issue 16
Reconciling the many faces of lateral gene transfer
journal, January 2002
- Lawrence, Jeffrey G.; Ochman, Howard
- Trends in Microbiology, Vol. 10, Issue 1
Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont
journal, June 2014
- Wakimoto, Toshiyuki; Egami, Yoko; Nakashima, Yu
- Nature Chemical Biology, Vol. 10, Issue 8
Synthesis of the C3–14 fragment of palmerolide A using a chiral pool based strategy
journal, February 2010
- Lebar, Matthew D.; Baker, Bill J.
- Tetrahedron, Vol. 66, Issue 8
Insights into the lifestyle of uncultured bacterial natural product factories associated with marine sponges
journal, January 2017
- Lackner, Gerald; Peters, Eike Edzard; Helfrich, Eric J. N.
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 3
Lobatamide C: Total Synthesis, Stereochemical Assignment, Preparation of Simplified Analogues, and V-ATPase Inhibition Studies
journal, June 2003
- Shen, Ruichao; Lin, Cheng Ting; Bowman, Emma Jean
- Journal of the American Chemical Society, Vol. 125, Issue 26
Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion
journal, November 2007
- Tatsuno, Satoshi; Arakawa, Kenji; Kinashi, Haruyasu
- The Journal of Antibiotics, Vol. 60, Issue 11
Chemical Synthesis and Biological Evaluation of Palmerolide A Analogues
journal, July 2008
- Nicolaou, K. C.; Leung, Gulice Y. C.; Dethe, Dattatraya H.
- Journal of the American Chemical Society, Vol. 130, Issue 30
The Interplay between a Multifunctional Dehydratase Domain and a C-Methyltransferase Effects Olefin Shift in Ambruticin Biosynthesis
journal, September 2016
- Berkhan, Gesche; Merten, Christian; Holec, Claudia
- Angewandte Chemie International Edition, Vol. 55, Issue 43
Direct Pathway Cloning (DiPaC) to unlock natural product biosynthetic potential
journal, May 2018
- Greunke, Christian; Duell, Elke Regina; D’Agostino, Paul Michael
- Metabolic Engineering, Vol. 47
Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus
journal, June 1998
- Quiros, Luis M.; Aguirrezabalaga, Ignacio; Olano, Carlos
- Molecular Microbiology, Vol. 28, Issue 6
Bacterial l-leucine catabolism as a source of secondary metabolites
journal, October 2015
- Díaz-Pérez, Alma L.; Díaz-Pérez, César; Campos-García, Jesús
- Reviews in Environmental Science and Bio/Technology, Vol. 15, Issue 1
Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases
journal, October 1995
- Haydock, Stephen F.; Aparicio, Jesús F.; Molnár, István
- FEBS Letters, Vol. 374, Issue 2
Evolution and Diversity of Assembly-Line Polyketide Synthases: Focus Review
journal, December 2019
- Nivina, Aleksandra; Yuet, Kai P.; Hsu, Jake
- Chemical Reviews, Vol. 119, Issue 24
Structure and Mechanism of the 6-Deoxyerythronolide B Synthase
journal, June 2007
- Khosla, Chaitan; Tang, Yinyan; Chen, Alice Y.
- Annual Review of Biochemistry, Vol. 76, Issue 1
Functional Characterization of Different ORFs Including Luciferase-Like Monooxygenase Genes from the Mensacarcin Gene Cluster
journal, April 2015
- Maier, Sarah; Heitzler, Tanja; Asmus, Katharina
- ChemBioChem, Vol. 16, Issue 8
Organization of the biosynthetic gene cluster for the macrolide concanamycin A in Streptomyces neyagawaensis ATCC 27449
journal, October 2005
- Haydock, Stephen F.; Appleyard, Anthony N.; Mironenko, Tatiana
- Microbiology, Vol. 151, Issue 10
Polyketide stereotetrads in natural products
journal, January 2005
- Koskinen, Ari M. P.; Karisalmi, Kaisa
- Chemical Society Reviews, Vol. 34, Issue 8
Increased Biosynthetic Gene Dosage in a Genome-Reduced Defensive Bacterial Symbiont
journal, November 2017
- Lopera, Juan; Miller, Ian J.; McPhail, Kerry L.
- mSystems, Vol. 2, Issue 6
Bacterial Biosynthetic Gene Clusters Encoding the Anti-cancer Haterumalide Class of Molecules
journal, November 2012
- Matilla, Miguel A.; Stöckmann, Henning; Leeper, Finian J.
- Journal of Biological Chemistry, Vol. 287, Issue 46
Formal Total Synthesis of Palmerolide A
journal, October 2012
- Pawar, Amit B.; Prasad, Kavirayani R.
- Chemistry - A European Journal, Vol. 18, Issue 47
Biosynthetic Pathway and Gene Cluster Analysis of Curacin A, an Antitubulin Natural Product from the Tropical Marine Cyanobacterium Lyngbya majuscula
journal, August 2004
- Chang, Zunxue; Sitachitta, Namthip; Rossi, James V.
- Journal of Natural Products, Vol. 67, Issue 8, p. 1356-1367
Marine natural products
journal, January 2019
- Carroll, Anthony R.; Copp, Brent R.; Davis, Rohan A.
- Natural Product Reports, Vol. 36, Issue 1
Automated structure prediction of trans-acyltransferase polyketide synthase products
journal, July 2019
- Helfrich, Eric J. N.; Ueoka, Reiko; Dolev, Alon
- Nature Chemical Biology, Vol. 15, Issue 8
Cloning and characterization of two genes from Streptomyces lividans that confer inducible resistance to lincomycin and macrolide antibiotics
journal, December 1991
- Jenkins, Gail; Cundliffe, Eric
- Gene, Vol. 108, Issue 1
The structures of type I polyketide synthases
journal, January 2012
- Keatinge-Clay, Adrian T.
- Natural Product Reports, Vol. 29, Issue 10
Iejimalides Show Anti-Osteoclast ActivityviaV-ATPase Inhibition
journal, June 2006
- Kazami, Sayaka; Muroi, Makoto; Kawatani, Makoto
- Bioscience, Biotechnology, and Biochemistry, Vol. 70, Issue 6
Assessment of Anabaena sp. Strain PCC 7120 as a Heterologous Expression Host for Cyanobacterial Natural Products: Production of Lyngbyatoxin A
journal, June 2016
- Videau, Patrick; Wells, Kaitlyn N.; Singh, Arun J.
- ACS Synthetic Biology, Vol. 5, Issue 9
Ancient Horizontal Gene Transfer from Bacteria Enhances Biosynthetic Capabilities of Fungi
journal, February 2009
- Schmitt, Imke; Lumbsch, H. Thorsten
- PLoS ONE, Vol. 4, Issue 2
Identification of the Putative Bryostatin Polyketide Synthase Gene Cluster from “ Candidatus Endobugula sertula”, the Uncultivated Microbial Symbiont of the Marine Bryozoan Bugula neritina
journal, December 2006
- Sudek, Sebastian; Lopanik, Nicole B.; Waggoner, Laura E.
- Journal of Natural Products, Vol. 70, Issue 1
The Final Steps of Bacillaene Biosynthesis in Bacillus amyloliquefaciens FZB42: Direct Evidence for β,γ Dehydration by a trans-Acyltransferase Polyketide Synthase
journal, January 2010
- Moldenhauer, Jana; Götz, Daniel C. G.; Albert, Christian R.
- Angewandte Chemie, Vol. 122, Issue 8
Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A and Isomers Thereof
journal, February 2008
- Nicolaou, K. C.; Sun, Ya-Ping; Guduru, Ramakrishna
- Journal of the American Chemical Society, Vol. 130, Issue 11
Computational Approach for Prediction of Domain Organization and Substrate Specificity of Modular Polyketide Synthases
journal, April 2003
- Yadav, Gitanjali; Gokhale, Rajesh S.; Mohanty, Debasisa
- Journal of Molecular Biology, Vol. 328, Issue 2
Isolation and Purification of a New Kalimantacin/Batumin-Related Polyketide Antibiotic and Elucidation of Its Biosynthesis Gene Cluster
journal, February 2010
- Mattheus, Wesley; Gao, Ling-Jie; Herdewijn, Piet
- Chemistry & Biology, Vol. 17, Issue 2
Characterization of the Polyoxin Biosynthetic Gene Cluster from Streptomyces cacaoi and Engineered Production of Polyoxin H
journal, April 2009
- Chen, Wenqing; Huang, Tingting; He, Xinyi
- Journal of Biological Chemistry, Vol. 284, Issue 16
The Phormidolide Biosynthetic Gene Cluster: Atrans-AT PKS Pathway Encoding a Toxic Macrocyclic Polyketide
journal, December 2015
- Bertin, Matthew J.; Vulpanovici, Alexandra; Monroe, Emily A.
- ChemBioChem, Vol. 17, Issue 2
A Shimizu Non-Aldol Approach to the Formal Total Synthesis of Palmerolide A
journal, September 2011
- Pujari, Sandip A.; Gowrisankar, Parthasarathy; Kaliappan, Krishna P.
- Chemistry - An Asian Journal, Vol. 6, Issue 11
Ecology of Antarctic Marine Sponges: An Overview
journal, April 2005
- McClintock, J. B.
- Integrative and Comparative Biology, Vol. 45, Issue 2
A Putative Gene Cluster from a Lyngbya wollei Bloom that Encodes Paralytic Shellfish Toxin Biosynthesis
journal, February 2011
- Mihali, Troco K.; Carmichael, Wayne W.; Neilan, Brett A.
- PLoS ONE, Vol. 6, Issue 2
Crossroads of Antibiotic Resistance and Biosynthesis
journal, August 2019
- Wencewicz, Timothy A.
- Journal of Molecular Biology, Vol. 431, Issue 18
MIBiG 2.0: a repository for biosynthetic gene clusters of known function
journal, October 2019
- Kautsar, Satria A.; Blin, Kai; Shaw, Simon
- Nucleic Acids Research
Palmerolide A, a Cytotoxic Macrolide from the Antarctic Tunicate Synoicum a dareanum
journal, May 2006
- Diyabalanage, Thushara; Amsler, Charles D.; McClintock, James B.
- Journal of the American Chemical Society, Vol. 128, Issue 17
Alteration of the Substrate Specificity of a Modular Polyketide Synthase Acyltransferase Domain through Site-Specific Mutations †
journal, December 2001
- Reeves, Christopher D.; Murli, Sumati; Ashley, Gary W.
- Biochemistry, Vol. 40, Issue 51
Total Synthesis and Structure Revision of the Marine Metabolite Palmerolide A
journal, April 2007
- Jiang, Xin; Liu, Bo; Lebreton, Sylvain
- Journal of the American Chemical Society, Vol. 129, Issue 20
Site-Specific Variability in the Chemical Diversity of the Antarctic Red Alga Plocamium cartilagineum
journal, June 2013
- Young, Ryan; von Salm, Jacqueline; Amsler, Margaret
- Marine Drugs, Vol. 11, Issue 6
Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection
journal, January 2008
- Nguyen, TuAnh; Ishida, Keishi; Jenke-Kodama, Holger
- Nature Biotechnology, Vol. 26, Issue 2
Formal Synthesis of Palmerolide A, Featuring Alkynogenic Fragmentation and syn-Selective Vinylogous Aldol Chemistry
journal, February 2013
- Lisboa, Marilda P.; Jones, David M.; Dudley, Gregory B.
- Organic Letters, Vol. 15, Issue 4
Inferring Horizontal Gene Transfer
journal, May 2015
- Ravenhall, Matt; Škunca, Nives; Lassalle, Florent
- PLOS Computational Biology, Vol. 11, Issue 5
Discovery of an Antarctic Ascidian-Associated Uncultivated
Verrucomicrobia
with Antimelanoma Palmerolide Biosynthetic Potential
journal, December 2021
- Murray, Alison E.; Lo, Chien-Chi; Daligault, Hajnalka E.
- mSphere, Vol. 6, Issue 6
Genomic and Metabolomic Insights into the Natural Product Biosynthetic Diversity of a Feral-Hog-Associated Brevibacillus laterosporus Strain
journal, March 2014
- Theodore, Christine M.; Stamps, Blake W.; King, Jarrod B.
- PLoS ONE, Vol. 9, Issue 3
The Biosynthetic Logic of Polyketide Diversity
journal, June 2009
- Hertweck, Christian
- Angewandte Chemie International Edition, Vol. 48, Issue 26
Palmerolide macrolides from the Antarctic tunicate Synoicum adareanum
journal, November 2011
- Noguez, Jaime H.; Diyabalanage, Thushara K. K.; Miyata, Yoshinari
- Bioorganic & Medicinal Chemistry, Vol. 19, Issue 22
Characterization of a Glycosyl Transferase Inactivating Macrolides, Encoded by
gimA
from
Streptomyces ambofaciens
journal, October 1998
- Gourmelen, Anne; Blondelet-Rouault, Marie-Hélène; Pernodet, Jean-Luc
- Antimicrobial Agents and Chemotherapy, Vol. 42, Issue 10
Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms
journal, August 2015
- Ueoka, Reiko; Uria, Agustinus R.; Reiter, Silke
- Nature Chemical Biology, Vol. 11, Issue 9
Rotation, Structure, and Classification of Prokaryotic V-ATPase
journal, December 2005
- Yokoyama, Ken; Imamura, Hiromi
- Journal of Bioenergetics and Biomembranes, Vol. 37, Issue 6
The Structure of a Ketoreductase Determines the Organization of the β-Carbon Processing Enzymes of Modular Polyketide Synthases
journal, April 2006
- Keatinge-Clay, Adrian T.; Stroud, Robert M.
- Structure, Vol. 14, Issue 4
Structure and Biosynthesis of the Jamaicamides, New Mixed Polyketide-Peptide Neurotoxins from the Marine Cyanobacterium Lyngbya majuscula
journal, June 2004
- Edwards, Daniel J.; Marquez, Brian L.; Nogle, Lisa M.
- Chemistry & Biology, Vol. 11, Issue 6
Heterologous Production of 4- O -Demethylbarbamide, a Marine Cyanobacterial Natural Product
journal, November 2012
- Kim, Eun Ji; Lee, Jong Hyun; Choi, Hyukjae
- Organic Letters, Vol. 14, Issue 23
Metamorphic enzyme assembly in polyketide diversification
journal, June 2009
- Gu, Liangcai; Wang, Bo; Kulkarni, Amol
- Nature, Vol. 459, Issue 7247
Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei
journal, November 2004
- Piel, J.; Hui, D.; Wen, G.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 46
The secret to a successful relationship: lasting chemistry between ascidians and their symbiotic bacteria
journal, October 2014
- Schmidt, Eric W.
- Invertebrate Biology, Vol. 134, Issue 1
Marine Macrolides, a Promising Source of Antitumor Compounds
journal, February 2009
- Napolitano, Jose G.; Daranas, Antonio H.; Norte, Manuel
- Anti-Cancer Agents in Medicinal Chemistry, Vol. 9, Issue 2
Evolutionary Implications of Bacterial Polyketide Synthases
journal, June 2005
- Jenke-Kodama, Holger; Sandmann, Axel; Müller, Rolf
- Molecular Biology and Evolution, Vol. 22, Issue 10
Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting
journal, May 2009
- Fisch, Katja M.; Gurgui, Cristian; Heycke, Nina
- Nature Chemical Biology, Vol. 5, Issue 7
Analysis of the Sorangicin Gene Cluster Reinforces the Utility of a Combined Phylogenetic/Retrobiosynthetic Analysis for Deciphering Natural Product Assembly by trans-AT PKS
journal, August 2010
- Irschik, Herbert; Kopp, Maren; Weissman, Kira J.
- ChemBioChem, Vol. 11, Issue 13
Peptide Bond Formation in Nonribosomal Peptide Biosynthesis: CATALYTIC ROLE OF THE CONDENSATION DOMAIN
journal, August 1998
- Stachelhaus, Torsten; Mootz, Henning D.; Bergendahl, Veit
- Journal of Biological Chemistry, Vol. 273, Issue 35
Thioesterases: A new perspective based on their primary and tertiary structures: Thioesterases: A New Perspective
journal, May 2010
- Cantu, David C.; Chen, Yingfei; Reilly, Peter J.
- Protein Science, Vol. 19, Issue 7
antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline
journal, April 2019
- Blin, Kai; Shaw, Simon; Steinke, Katharina
- Nucleic Acids Research, Vol. 47, Issue W1
Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A
journal, May 2010
- Erol , Özlem; Schäberle , Till F.; Schmitz, Alexander
- ChemBioChem, Vol. 11, Issue 9
Uncovering the Core Microbiome and Distribution of Palmerolide in Synoicum adareanum Across the Anvers Island Archipelago, Antarctica
journal, June 2020
- Murray, Alison E.; Avalon, Nicole E.; Bishop, Lucas
- Marine Drugs, Vol. 18, Issue 6
Characterization of the Microbial Community and Polyketide Biosynthetic Potential in the Palmerolide-Producing Tunicate Synoicum adareanum
journal, December 2008
- Riesenfeld, Christian S.; Murray, Alison E.; Baker, Bill J.
- Journal of Natural Products, Vol. 71, Issue 11
Unraveling the iterative type I polyketide synthases hidden in Streptomyces
journal, March 2020
- Wang, Bin; Guo, Fang; Huang, Chunshuai
- Proceedings of the National Academy of Sciences, Vol. 117, Issue 15
Polyketide β-Branching in Bryostatin Biosynthesis: Identification of Surrogate Acetyl-ACP Donors for BryR, an HMG-ACP Synthase
journal, October 2010
- Buchholz, Tonia J.; Rath, Christopher M.; Lopanik, Nicole B.
- Chemistry & Biology, Vol. 17, Issue 10
NRPSpredictor2—a web server for predicting NRPS adenylation domain specificity
journal, May 2011
- Röttig, Marc; Medema, Marnix H.; Blin, Kai
- Nucleic Acids Research, Vol. 39, Issue suppl_2
Oxazolomycin Biosynthesis in Streptomyces albus JA3453 Featuring an “Acyltransferase-less” Type I Polyketide Synthase That Incorporates Two Distinct Extender Units
journal, April 2010
- Zhao, Chunhua; Coughlin, Jane M.; Ju, Jianhua
- Journal of Biological Chemistry, Vol. 285, Issue 26
Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis
journal, February 2003
- Cheng, Y. -Q.; Tang, G. -L.; Shen, B.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 6
Biosynthesis of the Antibiotic Bacillaene, the Product of a Giant Polyketide Synthase Complex of thetrans-AT Family
journal, November 2007
- Moldenhauer, Jana; Chen, Xiao-Hua; Borriss, Rainer
- Angewandte Chemie International Edition, Vol. 46, Issue 43
A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis
journal, March 2009
- Lin, Shuangjun; Van Lanen, Steven G.; Shen, Ben
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 11
Synthetic Studies on a Marine Natural Product, Palmerolide A: Synthesis of C1-C9 and C15-C21 Fragments
journal, June 2007
- Kaliappan, Krishna; Gowrisankar, Parthasarathy
- Synlett, Vol. 2007, Issue 10
Mode of Cell Death Induction by Pharmacological Vacuolar H+-ATPase (V-ATPase) Inhibition
journal, January 2013
- von Schwarzenberg, Karin; Wiedmann, Romina M.; Oak, Prajakta
- Journal of Biological Chemistry, Vol. 288, Issue 2
Identification of a New Chondropsin Class of Antitumor Compound That Selectively Inhibits V-ATPases
journal, November 2003
- Bowman, Emma Jean; Gustafson, Kirk R.; Bowman, Barry J.
- Journal of Biological Chemistry, Vol. 278, Issue 45
Evolutionary dynamics at high latitudes: speciation and extinction in polar marine faunas
journal, November 2010
- Clarke, Andrew; Crame, J. Alistair
- Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 365, Issue 1558
Comparative Analysis of the Substrate Specificity of trans - versus cis- Acyltransferases of Assembly Line Polyketide Synthases
journal, June 2014
- Dunn, Briana J.; Watts, Katharine R.; Robbins, Thomas
- Biochemistry, Vol. 53, Issue 23
Structure–activity relationship study on 13-deoxytedanolide, a highly antitumor macrolide from the marine sponge Mycale adhaerens
journal, January 2005
- Nishimura, Shinichi; Matsunaga, Shigeki; Yoshida, Satoru
- Bioorganic & Medicinal Chemistry, Vol. 13, Issue 2
A Bidomain Nonribosomal Peptide Synthetase Encoded by FUM14 Catalyzes the Formation of Tricarballylic Esters in the Biosynthesis of Fumonisins
journal, February 2006
- Zaleta-Rivera, Kathia; Xu, Chunping; Yu, Fengan
- Biochemistry, Vol. 45, Issue 8