, Angew. Chem., Int. Ed, vol.48, p.4688, 2009.
, , p.113, 2009.
, J. Nat. Prod. Rep, p.996, 2010.
, , vol.393, p.31, 2007.
, ChemBioChem, vol.9, p.826, 2008.
, Nature, p.512, 2014.
, Nature, p.560, 2014.
, Science, vol.284, p.482, 1999.
, Biochemistry, vol.40, p.2326, 2001.
, Nat. Biotechnol, vol.23, p.1171, 2005.
, Chem. Biol, vol.14, p.143, 2007.
, Chem. Biol, p.1465, 2004.
, PLoS Comput. Biol, vol.3, p.186, 2007.
, Nat. Chem. Biol, 2008.
, J. Chem. Biol, vol.10, p.723, 2003.
, ACS Chem. Biol, vol.4, p.41, 2009.
, Chem. Biol, 1340.
, Proc. Natl. Acad. Sci. U. S. A, p.11124, 2006.
,
, Chem. Biol, vol.6, p.117, 1999.
, J. Chem. Sci, vol.5, p.3081, 2014.
, Angew. Chem., Int. Ed, 2011.
, Bioinformatics, vol.16, p.404, 2000.
, Methods Mol. Biol, p.263, 2014.
, Nat. Struct. Biol, vol.9, p.522, 2002.
27) Molecular Cloning: A Laboratory Manual; Sambrook, Nat. Chem. Biol, vol.8, p.615, 1989. ,
, Anal. Chem, vol.84, p.5066, 2012.
Protein NMR Spectroscopy: Principles and Practice, 1996. ,
Automated NMR Structure Calculation with CYANA, Protein NMR Techniques ,
Methods in Molecular Biology series, vol.278, pp.353-378, 2004. ,
, J. Mol. Biol, p.209, 2002.
, J. Biomol. NMR, p.213, 2009.
, , 2014.
, Journal of the American Chemical Society Article, vol.26, 1668.
, J. Am. Chem. Soc, vol.138, pp.4155-4167, 2016.
, Protein Eng., Des. Sel, 1992.
, J. Appl. Crystallogr, vol.42, p.892, 2009.
, Biochemistry, vol.35, 1996.
, Eur. J. Biochem, vol.267, p.520, 2000.
, J. Appl. Crystallogr, vol.25, p.495, 1992.
, J. Appl. Crystallogr, vol.43, p.231, 1997.
, Biophys. J, vol.76, p.2879, 1999.
, J. Appl. Crystallogr, vol.34, p.33, 2001.
, J. Appl. Crystallogr, vol.36, p.1277, 2003.
, J. Appl. Crystallogr, vol.36, p.860, 2003.
Small Angle X-Ray and Neutron Scattering from Solutions of Biological Macromolecules, 2013. ,
, Nucleic Acids Res, p.244, 2005.
, , vol.22, p.444, 2014.
, Current Protocols in Protein Science, 2007.
, Curr. Protein Pept. Sci, vol.28, issue.51, p.55, 1995.
, J. Mol. Biol, vol.215, p.403, 1990.
, Mol. Syst. Biol, 2011.
, Biochemistry, p.5056, 2002.
, Microb. Biotechnol, 2011.
, Nat. Biotechnol, vol.26, p.225, 2008.
, Biochem. Soc. Trans. 2012, vol.40, p.955
, J. Biomol. NMR, vol.14, issue.59, p.477, 1975.
, Acta Crystallogr., Sect. D: Biol. Crystallogr, p.12, 2010.
, Bioinformatics, vol.14, p.48, 1998.
, Nucleic Acids Res, p.545, 2010.
, Protein Sci, vol.22, p.693, 2013.
, Protein Sci, vol.23, p.539, 2014.
, Annu. Rev. Biochem, vol.83, p.553, 2014.
, Proteins: Struct., Funct, 2001.
, Chem. Rev, vol.109, p.839, 2009.
, Curr. Opin. Struct. Biol, 2011.
, J. Science, vol.252, p.1162, 1991.
, Biochem. Soc. Trans, vol.40, p.945, 2012.
, Journal of the American Chemical Society Article, vol.12, 2011.
, J. Am. Chem. Soc, vol.138, pp.4155-4167, 2016.
, Mol. Syst. Biol, 2011.
, Chem. Biol, 1340.
, J. Chem. Sci, vol.5, p.3081, 2014.
, J. Nat. Prod, vol.67, p.1356, 2004.
, ChemBioChem, vol.8, p.41, 2007.
, Chem. Biol, vol.10, p.419, 2003.
, Chem. Biol, vol.11, p.817, 2004.
, J. Biol. Chem, p.13082, 2002.
, Nat. Biotechnol, vol.26, p.225, 2008.
, ChemBioChem, vol.7, p.1206, 2006.
, Angew. Chem. Int. Ed Engl, vol.47, p.4595, 2008.
, Angew. Chem. Int. Ed Engl, vol.50, p.3882, 2011.
, , vol.393, p.31, 2007.
, Microb. Biotechnol, 2011.
, ACS Chem. Biol, vol.10, p.2468, 2015.
, ACS Chem. Biol, vol.10, p.2480, 2015.
, J. Biotechnol, p.174, 2006.
, , p.1253, 2010.
, J. Am. Chem. Soc, 2011.
, Chem. Biol, vol.15, p.175, 2008.
, J. Biol. Chem, p.39125, 2012.
, Z. J. Biol. Chem, p.285, 2010.
, J. Nat. Prod, vol.74, p.2031, 2011.
, PloS One, 2011.
, Chem. Biol, vol.18, p.665, 2011.
, Nat. Chem. Biol, vol.10, p.648, 2014.
, Andrésson, Ó. Proc. Natl. Acad. Sci. U. S. A, p.3129, 2013.
, Proc. Natl. Acad. Sci. U. S. A, vol.101, p.46, 2004.
, Proc. Natl. Acad. Sci. U. S. A, p.14002, 2002.
, Nat. Chem. Biol, vol.5, p.494, 2009.
, J. Nat. Prod, p.67, 2007.
, J. Am. Chem. Soc, p.14234, 2008.
, J. Proc. Natl. Acad. Sci. U. S. A, vol.104, p.1506, 2007.
, Chem. Biol, p.149, 2010.
, , p.91, 2005.
, ChemBioChem, vol.6, p.1277, 2005.
, , vol.13, p.416, 2012.
, J. Bacteriol, vol.188, p.4024, 2006.
, Proc. Natl. Acad. Sci. U. S. A, vol.100, p.3149, 2003.
, Nat. Chem. Biol, p.705, 2015.
, J. Nat. Prod, vol.70, p.1417, 2007.
, , p.1840, 2010.
, J. Nat. Prod, p.685, 2013.
, Chem. Biol, vol.19, p.1164, 2012.
, Biochemistry, vol.53, p.7854, 2014.
, Chem. Biol, vol.12, p.249, 2005.
, J. Biol. Chem, p.29746, 2009.
, Mol. Plant Microbe Interact, vol.17, p.414, 2004.
, J. Am. Chem. Soc, p.1155, 2013.
, Methods Mol. Biol, p.263, 2014.
, J. Appl. Crystallogr, vol.36, p.1277, 2003.
, J. Appl. Crystallogr, vol.25, p.495, 1992.
, Biophys. J, vol.76, p.2879, 1999.
, J. Appl. Crystallogr, vol.28, p.768, 1995.
ASSOCIATED REFERENCES, J. Appl. Cryst, vol.43, p.101, 2010. ,
, Bioinformatics, vol.21, p.3433, 2005.
, Bioinformatics, p.2745, 2009.
, Proteins, vol.42, p.38, 2001.
, Genome Inform. Workshop Genome Inform, vol.10, p.30, 1999.
, J. Mol. Biol, vol.337, p.635, 2004.
, Structure, vol.11, p.1453, 2003.
, BMC Bioinformatics, vol.12, p.66, 2011.
, J. Science, vol.252, p.1162, 1991.
, J. Chem. Biol, vol.10, p.723, 2003.
, , vol.3
, ACS Chem. Biol, vol.4, p.41, 2009.
, Mol. Syst. Biol, 2011.
, Chem. Biol, 1340.
Natural Product Derived Privileged Scaffolds in Drug Discovery, Curr Opin Chem Biol, vol.52, pp.1-8, 2019. ,
,
Polyketide Biosynthesis: A Millennium Review, Nat Prod Rep, vol.18, issue.4, pp.380-416, 2001. ,
Introduction to Polyketide Biosynthesis, Meth. Enzymol, vol.459, pp.3-16, 2009. ,
Evolutionary Implications of Bacterial Polyketide Synthases, Mol. Biol. Evol, vol.22, issue.10, pp.2027-2039, 2005. ,
Evolution of Metabolic Diversity: Insights from Microbial Polyketide Synthases. Phytochemistry, vol.70, pp.1858-1866, 2009. ,
Exploiting the Mosaic Structure of Trans-Acyltransferase Polyketide Synthases for Natural Product Discovery and Pathway Dissection, Nat. Biotechnol, vol.26, issue.2, pp.225-233, 2008. ,
Biosynthesis of Polyketides by Trans-AT Polyketide Synthases, Nat Prod Rep, vol.33, issue.2, pp.231-316, 2016. ,
Computational Identification and Analysis of Orphan Assembly-Line Polyketide Synthases, J. Antibiot, vol.67, issue.1, pp.89-97, 2014. ,
,
Post-PKS Tailoring Steps in Natural Product-Producing Actinomycetes from the Perspective of Combinatorial Biosynthesis, Nat Prod Rep, vol.27, issue.4, pp.571-616, 2010. ,
On-Line Enzymatic Tailoring of Polyketides and Peptides in Thiotemplate Systems, Curr Opin Chem Biol, vol.31, pp.82-94, 2016. ,
,
Genetic Engineering of Modular PKSs: From Combinatorial Biosynthesis to Synthetic Biology, Nat Prod Rep, 2015. ,
URL : https://hal.archives-ouvertes.fr/hal-01474079
Structure of a Modular Polyketide Synthase, Nature, vol.510, issue.7506, pp.512-517, 2014. ,
,
Structural Rearrangements of a Polyketide Synthase Module during Its Catalytic Cycle, Nature, vol.510, issue.7506, pp.560-564, 2014. ,
,
The Structure of Docking Domains in Modular Polyketide Synthases, Chem. Biol, vol.10, issue.8, pp.723-731, 2003. ,
Structural Basis for Binding Specificity between Subclasses of Modular Polyketide Synthase Docking Domains, ACS Chem. Biol, vol.4, issue.1, pp.41-52, 2009. ,
Cyanobacterial Polyketide Synthase Docking Domains: A Tool for Engineering Natural Product Biosynthesis, Chem. Biol, vol.20, issue.11, pp.1340-1351, 2013. ,
Multienzyme Docking in Hybrid Megasynthetases, Nat. Chem. Biol, vol.4, issue.1, pp.75-81, 2008. ,
,
,
Structure-Based Redesign of Docking Domain Interactions Modulates the Product Spectrum of a Rhabdopeptide-Synthesizing NRPS, Nat Commun, vol.9, issue.1, p.4366, 2018. ,
The Structural Basis for Docking in Modular Polyketide Biosynthesis, Chembiochem, vol.7, issue.3, pp.485-494, 2006. ,
Characterization of Intersubunit Communication in the Virginiamycin Trans-Acyl Transferase Polyketide Synthase, J. Am. Chem. Soc, 2016. ,
URL : https://hal.archives-ouvertes.fr/hal-01452317
Portability and Structure of the Four-Helix Bundle Docking Domains of Trans-Acyltransferase Modular Polyketide Synthases, ACS Chem. Biol, vol.2016, issue.9, pp.2466-2474 ,
Classification of Intrinsically Disordered Regions and Proteins, Chem. Rev, vol.114, issue.13, pp.6589-6631, 2014. ,
Mechanism of Intersubunit Ketosynthase-Dehydratase Interaction in Polyketide Synthases, Nat. Chem. Biol, vol.14, issue.3, pp.270-275, 2018. ,
,
Mechanism and Specificity of the Terminal Thioesterase Domain from the Erythromycin Polyketide Synthase, Chem. Biol, vol.6, issue.2, pp.117-125, 1999. ,
, , pp.80008-80016
Transient Protein-Protein Interactions, Protein Eng. Des. Sel, vol.24, issue.9, pp.635-648, 2011. ,
,
Structural Characterisation and Functional Significance of Transient Protein-Protein Interactions, J. Mol. Biol, vol.325, issue.5, pp.991-1018, 2003. ,
Enacyloxins Are Products of an Unusual Hybrid Modular Polyketide Synthase Encoded by a Cryptic Burkholderia Ambifaria Genomic Island, Chem. Biol, vol.18, issue.5, pp.665-677, 2011. ,
, 2017-Who-Publishes-List-of-Bacteria-for-Which-New-Antibiotics-Are-Urgently-Needed
Minimum Information about a Biosynthetic Gene Cluster, Nat. Chem. Biol, vol.11, issue.9, pp.625-631, 2015. ,
URL : https://hal.archives-ouvertes.fr/hal-01430728
,
A Dual Transacylation Mechanism for Polyketide Synthase Chain Release ,
The PSIPRED Protein Analysis Workbench: 20 Years On, Nucleic Acids Res ,
Context-Dependent Prediction of Protein Disorder as a Function of Redox State and Protein Binding, Nucleic Acids Res, vol.46, issue.W1, pp.329-337, 2018. ,
Predicting Coiled Coils from Protein Sequences, Science, vol.252, issue.5009, pp.1162-1164, 1991. ,
, Protein Identification and Analysis Tools in the ExPASy Server, 2019.
How Random Are Intrinsically Disordered Proteins? A Small Angle Scattering Perspective, Curr. Protein Pept. Sci, vol.2012, issue.1, pp.55-75 ,
Quantitative Analysis of Protein Far UV Circular Dichroism Spectra by Neural Networks, Protein Eng, vol.5, issue.3, pp.191-195, 1992. ,
A Decade and a Half of Protein Intrinsic Disorder, Biology Still Waits for Physics. Protein Sci, vol.2013, issue.6, pp.693-724 ,
Assessing Coupled Protein Folding and Binding Through Temperature-Dependent Isothermal Titration Calorimetry, Meth. Enzymol, vol.567, pp.23-45, 2016. ,
,
Automated NMR Structure Calculation with CYANA, Methods Mol. Biol, vol.278, pp.353-378, 2004. ,
, , p.353
, Jun, vol.22, 2018.
The Amber Biomolecular Simulation Programs, J Comput Chem, vol.26, issue.16, pp.1668-1688, 2005. ,
,
Programs for Checking the Quality of Protein Structures Solved by NMR, J. Biomol. NMR, vol.8, issue.4, pp.477-486, 1996. ,
MolProbity: All-Atom Structure Validation for Macromolecular Crystallography, Acta Crystallogr. D Biol. Crystallogr, pp.12-21, 2010. ,
Insights into Coupled Folding and Binding Mechanisms from Kinetic Studies, J. Biol. Chem, issue.13, pp.6689-6695, 2016. ,
,
The C-Terminal Domain of the Measles Virus Nucleoprotein Is Intrinsically Disordered and Folds upon Binding to the C-Terminal Moiety of the Phosphoprotein, J. Biol. Chem, vol.278, issue.20, pp.18638-18648, 2003. ,
,
The Missing Linker: A Dimerization Motif Located within Polyketide Synthase Modules, ACS Chem. Biol, vol.8, issue.6, pp.1263-1270, 2013. ,
Molecular Analysis of the Kirromycin Biosynthetic Gene Cluster Revealed Beta-Alanine as Precursor of the Pyridone Moiety, Chem. Biol, vol.15, issue.2, pp.175-188, 2008. ,
,
, Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment. Front. Mol. Biosci, 2016.
Functional Dissection of a Multimodular Polypeptide of the Pikromycin Polyketide Synthase into Monomodules by Using a Matched Pair of Heterologous Docking Domains, Chembiochem, vol.10, issue.9, pp.1537-1543, 2009. ,
,
Solution Structure and Proposed Domain Domain Recognition Interface of an Acyl Carrier Protein Domain from a Modular Polyketide Synthase. Protein Sci, vol.16, pp.2093-2107, 2007. ,
Insights into the Function of Trans-Acyl Transferase Polyketide Synthases from the SAXS Structure of a Complete Module, Chem. Sci, vol.2014, issue.8, pp.3081-3095 ,
URL : https://hal.archives-ouvertes.fr/hal-01453210
The 2.7-Angstrom Crystal Structure of a 194-KDa Homodimeric Fragment of the 6-Deoxyerythronolide B Synthase, Proc. Natl. Acad. Sci. U.S.A, vol.103, issue.30, pp.11124-11129, 2006. ,
URL : https://hal.archives-ouvertes.fr/in2p3-00003512
,
A Close Look at a Ketosynthase from a Trans-Acyltransferase Modular Polyketide Synthase, Structure, vol.22, issue.3, pp.444-451, 2014. ,
The Structure of a Ketoreductase Determines the Organization of the Beta-Carbon Processing Enzymes of Modular Polyketide Synthases, Structure, vol.14, issue.4, pp.737-748, 2006. ,
A Tylosin Ketoreductase Reveals How Chirality Is Determined in Polyketides, Chem. Biol, vol.14, issue.8, pp.898-908, 2007. ,
Molecular Cloning: A Laboratory Manual. Molecular cloning: a laboratory manual, 1989. ,
High-Precision Isothermal Titration Calorimetry with Automated Peak-Shape Analysis, Anal. Chem, vol.2012, issue.11, pp.5066-5073 ,
, Protein NMR Spectroscopy
, , 2007.
Protein NMR Structure Determination with Automated NOE Assignment Using the New Software CANDID and the Torsion Angle Dynamics Algorithm DYANA, J Mol Biol, vol.319, issue.1, pp.241-244, 2002. ,
Protein Backbone and Sidechain Torsion Angles Predicted from NMR Chemical Shifts Using Artificial Neural Networks, J. Biomol. NMR, vol.2013, issue.3, pp.227-241 ,
,
Combined Sampler Robot and High-Performance Liquid Chromatography: A Fully Automated System for Biological Small-Angle X-Ray Scattering Experiments at the Synchrotron SOLEIL SWING Beamline, J Appl Cryst, vol.42, issue.5, pp.892-900, 2009. ,
,
Determination of the Regularization Parameter in Indirect-Transform Methods Using Perceptual Criteria, J Appl Crystallogr, vol.25, issue.4, pp.495-503, 1992. ,
Determination of the Molecular Weight of Proteins in Solution from a Single Small-Angle X-Ray Scattering Measurement on a Relative Scale, J. Appl. Cryst, vol.43, pp.101-109, 2010. ,
Absolute Molecular Weight Distribution of Low-Molecular-Weight Heparins by Size-Exclusion Chromatography with Multiangle Laser Light Scattering Detection, Anal. Biochem, vol.245, issue.2, pp.231-241, 1997. ,
,
Restoring Low Resolution Structure of Biological Macromolecules from Solution Scattering Using Simulated Annealing, Biophysical Journal, vol.76, issue.6, pp.2879-2886, 1999. ,
, , pp.77443-77449
Automated Matching of High-and Low-Resolution Structural Models, J Appl Crystallogr, vol.34, issue.1, pp.33-41, 2001. ,
PRIMUS: A Windows PC-Based System for Small-Angle Scattering Data Analysis, J Appl Crystallogr, vol.36, issue.5, pp.1277-1282, 2003. ,
,
Insights into the Function of Trans-Acyl Transferase Polyketide Synthases from the SAXS Structure of a Complete Module, Chem. Sci, vol.2014, issue.8, pp.3081-3095 ,
URL : https://hal.archives-ouvertes.fr/hal-01453210
The 2.7-Angstrom Crystal Structure of a 194-KDa Homodimeric Fragment of the 6-Deoxyerythronolide B Synthase, Proc. Natl. Acad. Sci. U. S. A, vol.103, issue.30, pp.11124-11129, 2006. ,
URL : https://hal.archives-ouvertes.fr/in2p3-00003512
Enacyloxins Are Products of an Unusual Hybrid Modular Polyketide Synthase Encoded by a Cryptic Burkholderia Ambifaria Genomic Island, Chem. Biol, vol.18, issue.5, pp.665-677, 2011. ,
Structural and Mechanistic Analysis of Protein Interactions in Module 3 of the 6-Deoxyerythronolide B Synthase, Chem. Biol, vol.14, issue.8, pp.931-943, 2007. ,
The PSIPRED Protein Analysis Workbench: 20 Years On, Nucleic Acids Res ,
Structural and Functional Studies of a Trans-Acyltransferase Polyketide Assembly Line Enzyme That Catalyzes Stereoselective ?-and ?-Ketoreduction, Proteins, vol.82, issue.9, pp.2067-2077, 2014. ,
A Tylosin Ketoreductase Reveals How Chirality Is Determined in Polyketides, Chem. Biol, vol.14, issue.8, pp.898-908, 2007. ,
Structural and Functional Analysis of A-Type Ketoreductases from the Amphotericin Modular Polyketide Synthase, Struct. Lond. Engl, vol.18, issue.8, pp.913-922, 1993. ,
The Structure of a Ketoreductase Determines the Organization of the Beta-Carbon Processing Enzymes of Modular Polyketide Synthases, Struct. Lond. Engl, vol.14, issue.4, pp.737-748, 1993. ,
Supramolecular Templating in Kirromycin Biosynthesis: The Acyltransferase KirCII Loads Ethylmalonyl-CoA Extender onto a Specific ACP of the Trans-AT PKS, Chem. Biol, vol.18, issue.4, pp.438-444, 2011. ,
IUPred2A: Context-Dependent Prediction of Protein Disorder as a Function of Redox State and Protein Binding, Nucleic Acids Res, vol.46, issue.W1, pp.329-337, 2018. ,
Determination of the Regularization Parameter in Indirect-Transform Methods Using Perceptual Criteria, J. Appl. Crystallogr, vol.25, issue.4, pp.495-503, 1992. ,
Restoring Low Resolution Structure of Biological Macromolecules from Solution Scattering Using Simulated Annealing, Biophys. J, vol.76, issue.6, pp.77443-77449, 1999. ,
PRIMUS: A Windows PC-Based System for Small-Angle Scattering Data Analysis, J. Appl. Crystallogr, vol.36, issue.5, pp.1277-1282, 2003. ,
Uniqueness of ab initio shape determination in small, 2019. ,
Automated Matching of High-and Low-Resolution Structural Models, J. Appl. Crystallogr, vol.34, issue.1, pp.33-41, 2001. ,
Global Rigid Body Modeling of Macromolecular Complexes against Small-Angle Scattering Data, Biophys. J, vol.89, issue.2, pp.1237-1250, 2005. ,
CRYSOL -a Program to Evaluate X-Ray Solution Scattering of Biological Macromolecules from Atomic Coordinates, J. Appl. Crystallogr, vol.28, issue.6, pp.768-773, 1995. ,
Determination of the Molecular Weight of Proteins in Solution from a Single Small-Angle X-Ray Scattering Measurement on a Relative Scale, J Appl Cryst, vol.43, pp.101-109, 2010. ,
Accurate Assessment of Mass, Models and Resolution by Small-Angle Scattering, Nature, vol.2013, issue.7446, pp.477-481 ,
Programs for Checking the Quality of Protein Structures Solved by NMR, J. Biomol. NMR, vol.8, issue.4, pp.477-486, 1996. ,
MolProbity: All-Atom Structure Validation for Macromolecular Crystallography, Acta Crystallogr. D Biol. Crystallogr, pp.12-21, 2010. ,
The Structure of Docking Domains in Modular Polyketide Synthases, Chem. Biol, vol.10, issue.8, pp.723-731, 2003. ,
Structural Basis for Binding Specificity between Subclasses of Modular Polyketide Synthase Docking Domains, ACS Chem. Biol, vol.4, issue.1, pp.41-52, 2009. ,
Cyanobacterial Polyketide Synthase Docking Domains: A Tool for Engineering Natural Product Biosynthesis, Chem. Biol, vol.20, issue.11, pp.1340-1351, 2013. ,
Characterization of Intersubunit Communication in the Virginiamycin Trans-Acyl Transferase Polyketide Synthase, J. Am. Chem. Soc, 2016. ,
URL : https://hal.archives-ouvertes.fr/hal-01452317
Portability and Structure of the Four-Helix Bundle Docking Domains of Trans-Acyltransferase Modular Polyketide Synthases, ACS Chem. Biol, vol.2016, issue.9, pp.2466-2474 ,
Understanding enzyme function evolution from a computational perspective, Curr. Opin. Struct. Biol, vol.47, pp.131-139, 2017. ,
,
Large-scale analysis exploring evolution of catalytic machineries and mechanisms in enzyme superfamilies, J. Mol. Biol, vol.428, pp.253-267, 2016. ,
Filling out the structural map of the NTF2-like superfamily, BMC Bioinformatics, vol.14, p.327, 2013. ,
The fumarylacetoacetate hydrolase (FAH) superfamily of enzymes: multifunctional enzymes from microbes to mitochondria, Biochem. Soc. Trans, vol.46, pp.295-309, 2018. ,
Divergent evolution in enolase superfamily: strategies for assigning functions, J. Biol. Chem, vol.287, pp.29-34, 2012. ,
Polyketide biosynthesis: a millennium review, Nat. Prod. Rep, vol.18, pp.380-416, 2001. ,
Polyketide synthase and nonribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate?, Nat. Prod. Rep, vol.33, pp.183-202, 2016. ,
Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei, Chem. Biol, vol.12, pp.249-256, 2005. ,
Structures and mechanism of the monoamine oxidase family, Biomol. Concepts, vol.2, pp.365-377, 2011. ,
Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation of fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the flavoenzyme Af12070 from Aspergillus fumigatus, Biochemistry, vol.50, pp.8756-8769, 2011. ,
Biocatalytic asymmetric Mannich reaction of ketimines using wheat germ lipase, Catal. Sci. Technol, vol.6, pp.3963-3970, 2016. ,
Sequence-structure analysis of FAD-containing proteins, Protein Sci, vol.10, pp.1712-1728, 2001. ,
Dali server: conservation mapping in 3D, Nucleic Acids Res, vol.38, pp.545-549, 2010. ,
Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase (MAO) family, Proc. Natl. Acad. Sci. USA, vol.108, pp.4800-4805, 2011. ,
Structure of human monoamine oxidase A at 2.2-Å resolution: the control of opening the entry for substrates/inhibitors, Proc. Natl. Acad. Sci. USA 105, pp.5739-5744, 2008. ,
Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders, Nat. Struct. Biol, vol.9, pp.22-26, 2002. ,
Structural insight into unique properties of protoporphyrinogen oxidase from Bacillus subtilis, J. Struct. Biol, vol.170, pp.76-82, 2010. ,
Structure and mechanism of the Propionibacterium acnes polyunsaturated fatty acid isomerase, Proc. Natl. Acad. Sci. USA, vol.103, pp.2576-2581, 2006. ,
CATH: comprehensive structural and functional annotations for genome sequences, Nucleic Acids Res, vol.43, pp.376-381, 2015. ,
, Comprehensive Natural Products II: Chemistry and Biology, pp.37-113, 2010.
PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin, Proc. Natl. Acad. Sci. USA, vol.100, pp.1541-1546, 2003. ,
An additional dehydratase-like activity is required for lankacidin antibiotic biosynthesis, Chembiochem, vol.12, pp.2408-2412, 2011. ,
Two new lankacidin-related metabolites from Streptomyces sp. HS-NF-1178, J. Antibiot, vol.71, pp.397-401, 2018. ,
Purification and analysis of streptococcal NADH peroxidase expressed in Escherichia coli, J. Biol. Chem, vol.268, pp.3161-3167, 1993. ,
In vitro reconstitution and analysis of the 6-deoxyerythronolide B synthase, J. Am. Chem. Soc, vol.135, pp.16809-16812, 2013. ,
A twisted base? The role of arginine in enzyme-catalyzed proton abstractions, Arch. Biochem. Biophys, vol.433, pp.266-278, 2005. ,
A natural prodrug activation mechanism in the biosynthesis of nonribosomal peptides, Nat. Prod. Rep, vol.31, pp.154-159, 2014. ,
Enzyme engineering: rational redesign versus directed evolution, Trends Biotechnol, vol.19, pp.13-14, 2001. ,
Recent advances in rational approaches for enzyme engineering, Comput. Struct. Biotechnol. J, vol.2, p.201209010, 2012. ,
Basic local alignment search tool, J. Mol. Biol, vol.215, pp.403-410, 1990. ,
Molecular Cloning: A Laboratory Manual 3rd edn, 2000. ,
, Practical Streptomyces Genetics (The John Innes Foundation, 2000.
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products, Proc. Natl. Acad. Sci. USA, vol.97, pp.6640-6645, 2000. ,
Experimental phasing: substructure solution and density modification as implemented in SHELX, Methods Mol. Biol, vol.1607, pp.357-376, 2017. ,
The Buccaneer software for automated model building. 1. Tracing protein chains, Acta Crystallogr. D. Biol. Crystallogr, vol.62, pp.1002-1011, 2006. ,
Fitting molecular fragments into electron density, Acta Crystallogr. D. Biol. Crystallogr, vol.64, pp.83-89, 2008. ,
Coot: model-building tools for molecular graphics, Acta Crystallogr. D. Biol. Crystallogr, vol.60, pp.2126-2132, 2004. ,
BUSTER version 2.10.2.(Global Phasing Ltd, 2017. ,
Phaser crystallographic software, J. Appl. Crystallogr, vol.40, pp.658-674, 2007. ,
MolProbity: all-atom structure validation for macromolecular crystallography, Acta Crystallogr. D. Biol. Crystallogr, vol.66, pp.12-21, 2010. ,
Analysis of modular-iterative mixed biosynthesis of lankacidin by heterologous expression and gene fusion, J. Antibiot, vol.60, pp.700-708, 2007. ,
An unusual dehydratase acting on glycerate and a ketoreductase stereoselectively reducing ?-ketone in polyketide starter unit biosynthesis, Angew. Chem. Int. Ed. Engl, vol.53, pp.11315-11319, 2014. ,
Determination of domain structure of proteins from X-ray solution scattering, Biophys. J, vol.80, pp.2946-2953, 2001. ,
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice, Nucleic Acids Res, vol.22, pp.4673-4680, 1994. ,
ESPript/ENDscript: Extracting and rendering sequence and 3D information from atomic structures of proteins, Nucleic Acids Res, vol.31, pp.3320-3323, 2003. ,
URL : https://hal.archives-ouvertes.fr/hal-00314281
CRYSOL -a program to evaluate X-ray solution scattering of biological macromolecules from atomic coordinates, J. Appl. Crystallogr, vol.28, pp.768-773, 1995. ,
Determination of the molecular weight of proteins in solution from a single small-angle X-ray scattering measurement on a relative scale, J. Appl. Cryst, vol.43, pp.101-109, 2010. ,
Determination of the regularization parameter in indirecttransform methods using perceptual criteria, J. Appl. Crystallogr, vol.25, pp.495-503, 1992. ,
Automated matching of high-and lowresolution structural models, J. Appl. Crystallogr, vol.34, pp.33-41, 2001. ,
, Analysis of extracts of an in vitro assay containing inactivated LkcE and purified 6. Trace of the absorbance at 230 nm, showing a single peak at RT = 15.0 min corresponding to 6 (greyed). (b) Analysis at m/z = 462 (ESI negative) of the same in vitro assay yields a single peak at RT = 15.2 min (greyed). (c) Trace of the absorbance at 230 nm of extracts of wild type S. rochei, showing the absence of a significant peak at RT = 15.0 min. (d) Analysis of wild type S. rochei at m/z = 462 (ESI negative) also did not reveal any peak corresponding to 6. (e) Trace of the absorbance at 230 nm of extracts of the ?lkcE inactivation mutant. Two candidate peaks corresponding to 6 are observed (greyed). (f) Analysis of the ?lkcE inactivation mutant at m/z = 462 (ESI negative) reveals two candidate peaks corresponding to 6 with the same, Supplementary Figure 8 ? Analysis by HPLC-MS of extracts of wild type S. rochei vs. the ?lkcE inactivation mutant for LC-KA05 (1) and downstream products, cont. (i)?(w) Analysis for metabolites formed downstream of LC-KA05. (i)?(m) Analysis for lankacidinol A (2) (exact mass = 503.25 Da). (i) Trace of the absorbance at 230 nm of extracts of the wild type. (j) SIM of m/z = 504 (ESI positive) of extracts of the wild type
, Supplementary Figure 12 ? Demonstration by HPLC-MS that LkcE is active in vitro, cont. (p) at RT =15 min, as observed in the control. (u) Analysis of the LkcE reaction at m/z = 460 for 9
, Mass spectrum (ESI negative) of the peak at RT = 17.5 in (u) yields peaks consistent with 9
, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.1541-1546, 2003.
, ChemBioChem, vol.12, pp.2408-2412, 2011.
, Chem. Biol, vol.12, pp.249-256, 2005.
, J. Mol. Biol, vol.215, pp.403-410, 1990.
, J. Antibiot, 2018.
, Proc. Natl. Acad. Sci. U. S. A, vol.108, pp.4800-4805, 2011.
, Nat. Struct. Biol, vol.9, pp.22-26, 2002.
Fungal polyketide engineering comes of age, Proc. Natl ,
, > Alberts A. W. « Discovery, biochemistry and biology of lovastatin, vol.111, pp.10-15, 1988.
« Solution structure and proposed domain-domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase, Protein Sci, vol.16, pp.2093-2107, 2007. ,
,
, « Complexity Generation in Fungal Peptidyl Alkaloid Biosynthesis: Oxidation of
, Fumiquinazoline A to the Heptacyclic Hemiaminal Fumiquinazoline C by the Flavoenzyme Af12070 from Aspergillus fumigatus ». Biochemistry, vol.50, pp.8756-8769, 2011.
, ChemBioChem, vol.16, pp.1357-1364, 2015.
Organization of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of the enzymatic domains in the modular polyketide synthase ,
, , vol.169, pp.9-16
Butyrolactone autoregulator-receptor system involved in lankacidin and lankamycin production and morphological differentiation in Streptomyces rochei ». Microbiology [En ligne, vol.153, pp.1817-1827, 2007. ,
« Cyclization Mechanism for the Synthesis of Macrocyclic Antibiotic Lankacidin in Streptomyces rochei, Chem. Biol, vol.12, pp.249-256, 2005. ,
,
, The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics ». Proc. Natl. Acad. Sci, vol.107, pp.1983-1988, 2010.
Directed Mutagenesis Alters the Stereochemistry of Catalysis by Isolated Ketoreductase Domains from the Erythromycin Polyketide Synthase ,
Is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration?, J. Ind. Microbiol. Biotechnol, vol.13, pp.277-285, 2006. ,
, , vol.33, pp.507-513
, Cryptic Polyketide Synthase Genes in Non-Pathogenic
, , vol.7, p.29609, 2012.
« Crystal structure of the synergistic antibiotic pair, lankamycin and lankacidin, in complex with the large ribosomal subunit, Proc. Natl. Acad. Sci ,
, , vol.108, pp.2717-2722
Leadlay P. F. « 6-Deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea. Cloning of the structural gene, sequence analysis and inferred domain structure of the multifunctional enzyme, Eur. J. Biochem, 1992. ,
Mutagenesis of the dehydratase active site in the erythromycin-producing polyketide synthase, Biochem. Soc. Trans, vol.204, p.30, 1993. ,
, Studies in relation to biosynthesis
, VII. 2-Hydroxy-6-methylbenzoic acid in Penicillium griseofulvum Dierckx », Aust. J. Chem
, , vol.8, pp.539-544
Conformational flexibility of metazoan fatty acid synthase enables catalysis, Nat. Struct. Mol. Biol, vol.3, pp.190-197, 2009. ,
, « The structure of docking domains in modular polyketide synthases, vol.10, pp.723-731
, The PSIPRED Protein Analysis Workbench: 20 years on, vol.47, pp.402-407, 2019.
A. « A ketoreductase domain in the PksJ protein of the bacillaene assembly line carries out both ?-and ?-ketone reduction during chain growth, Conserved Amino Acid Residues Correlating With Ketoreductase Stereospecificity in Modular Polyketide Synthases, vol.4, pp.3149-3154, 2003. ,
, Antibiotics of the Virginiamycin Family, Inhibitors Which Contain Synergistic Components, vol.43, p.281470, 1979.
An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea », Nature, vol.348, pp.176-178, 1990. ,
« Combined sampler robot and high-performance liquid chromatography: a fully automated system for biological small-angle X-ray scattering experiments at the Synchrotron SOLEIL SWING beamline, J. Appl. Crystallogr ,
, , vol.42, pp.892-900
« Origins and evolution of antibiotic resistance ,
, Biol. Rev. MMBR, vol.74, pp.417-433, 2010.
,
Insights into the function of trans-acyl transferase polyketide synthases from the SAXS structure of a complete module, Chem Sci, vol.5, pp.3081-3095, 2014. ,
,
Demain A. L. « Importance of microbial natural products and the need to revitalize their discovery, J. Ind. Microbiol. Biotechnol, vol.30, pp.185-201, 2003. ,
,
Fang A. « The natural functions of secondary metabolites ,
, Biochem. Eng. Biotechnol. 2001, vol.69, pp.1-39
Improved Bioconversion of 15-Fluoro-6-deoxyerythronolide B to 15-Fluoro-erythromycin A by Overexpression of the eryK Gene in Saccharopolyspora erythraea, Biotechnol. Prog, vol.20, pp.2408-2412, 2004. ,
, Gene, vol.111, pp.51-60, 1992.
« Modular organization of genes required for complex polyketide biosynthesis, Proc. Natl. Acad. Sci. 1993, vol.90, pp.675-679, 1991. ,
,
, Characterization of Intersubunit Communication in the Virginiamycin trans
URL : https://hal.archives-ouvertes.fr/hal-01735993
« Comparative Analysis of the Substrate Specificity of trans -versus cis-Acyltransferases of Assembly Line Polyketide Synthases, J. R. Soc. Interface, vol.138, pp.3796-3806, 2013. ,
« Structure of a modular polyketide synthase », Nature, vol.510, pp.512-517, 2014. ,
« Architectures of Whole-Module and Bimodular Proteins from the 6-Deoxyerythronolide B Synthase, J. Mol. Biol ,
, , vol.426, pp.2229-2245, 2014.
A. « Comprehensive Natural Products II, Compr. Nat. Prod ,
URL : https://hal.archives-ouvertes.fr/hal-02436139
, , pp.37-114, 2010.
Antibiotics for emerging pathogens, 2009. ,
Assembly-Line Enzymology for Polyketide and Nonribosomal Peptide Antibiotics: Logic, Machinery, and Mechanisms », > Fitzpatrick P. F. « Oxidation of amines by flavoproteins, vol.325, pp.13-25, 2006. ,
, , vol.51, pp.1-8, 2019.
,
Parallel pathways for oxidation of 14-membered polyketide macrolactones in Saccharopolyspora erythraea: Hybrid macrolide biosynthesis in S. erythraea, « Malleable machines take shape in eukaryotic transcriptional regulation, vol.4, pp.771-781, 2002. ,
Elucidation of the Cryptic Epimerase Activity of Redox-Inactive Ketoreductase Domains from Modular Polyketide Synthases by Tandem Equilibrium Isotope Exchange, J. Am. Chem. Soc, vol.135, pp.16324-16327, 2013. ,
, , vol.136, pp.10190-10193
, « The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex, J. Struct. Biol, vol.193, pp.196-205, 2016.
Effect of CO(2) enrichment on synthesis of some primary and secondary metabolites in ginger, Int. J. Mol. Sci, vol.12, pp.1101-1114, 2011. ,
, Synthetic Polyketide Enzymology: Platform for Biosynthesis of Antimicrobial Polyketides, vol.5, pp.4033-4042, 2015.
, Science, vol.284, pp.482-485, 1999.
,
Mutasynthesis of Rapamycin Analogues through the Manipulation of a ,
, Gene Governing Starter Unit Biosynthesis, vol.44, pp.4757-4760, 2005.
Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS, Nat. Commun, vol.9, 2018. ,
Analysis of Acyl Transferase Domain Exchange in Polyketide Synthase Modules, J. Am. Chem. Soc, vol.125, pp.5366-5374, 2003. ,
, Peptidyl Transferase Center of the Large Ribosomal Subunit ». J. Mol. Biol, 2003.
, , vol.330, pp.1061-1075
« In vitro and in vivo activities of sedecamycin against Treponema hyodysenteriae, Antimicrob. Agents Chemother ,
« Formation of the Aureothin Tetrahydrofuran Ring by a Bifunctional Cytochrome P450 Monooxygenase, Biosynthesis of polyketides by trans-AT polyketide synthases, vol.32, pp.162-190, 1998. ,
, , vol.5, pp.35-47
The changing patterns of covalent active site occupancy during catalysis on a modular polyketide synthase multienzyme revealed by iontrap mass spectrometry: Changing patterns of covalent active-site occupancy, vol.276, pp.7057-7069, 2009. ,
Acinetobacter baumannii: An emerging opportunistic pathogen, vol.3, pp.243-250, 2012. ,
,
« Structure-Guided Programming of Polyketide Chain-Length Determination in Chalcone Synthase, Interaction between Polyketide Synthase and Transporter Suggests Coupled Synthesis and Export of Virulence Lipid in M. tuberculosis ». PLoS Pathog, vol.1, pp.14829-14838, 2001. ,
, Biosynthesis, Classification, Function and Pharmacological Properties », J. Pharm. Pharmacol
,
Engineering the Substrate Specificity of a Modular Polyketide Synthase for Installation of Consecutive Non-Natural Extender Units, J. Am. Chem. Soc, vol.141, pp.1961-1969, 2019. ,
Engineered Biosynthesis of an Eight-Membered Ring Tetraketide Lactone, J. Am. Chem. Soc, vol.119, pp.11339-11340, 1997. ,
, , vol.43, pp.155-176, 2016.
Structure of the Erythromycin Polyketide Synthase ,
, J. Mol. Biol, vol.384, pp.941-953, 2008.
Ketoreductase Reveals How Chirality Is Determined in Polyketides, Nat. Struct. Mol. Biol, vol.14, pp.888-893, 2004. ,
A Polylinker Approach to Reductive Loop Swaps in Modular Polyketide Synthases, Structure, vol.14, pp.2740-2749, 2006. ,
,
Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis ». Microb. Cell Factories, vol.16, 2017. ,
,
« Isolation and characterization of linear plasmids from lankacidin-producing Streptomyces species, J. Antibiot. (Tokyo), vol.47, pp.2004-2021, 1994. ,
,
« Inversion of Extender Unit Selectivity in the Erythromycin Polyketide Synthase by Acyltransferase Domain Engineering, ACS Chem. Biol ,
Protein-protein interactions in trans-AT polyketide synthases, Nat. Prod. Rep, vol.12, pp.1097-1109, 2018. ,
« Structural basis for chain release from the enacyloxin polyketide synthase », Nat. Chem, vol.11, pp.913-923, 2019. ,
,
Mutagenesis Gives Rise to a Biosynthetic Polyketide Library ,
, , vol.51, pp.10664-10669, 2012.
, « Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens, Proc. Natl. Acad. Sci, 2011.
« The role of erythromycin C-12 hydroxylase, EryK, as a substitute for PikC hydroxylase in pikromycin biosynthesis, vol.108, pp.549-559, 2004. ,
« Construction of a New Class of, Tetracycline Lead Structures with Potent Antibacterial Activity through Biosynthetic Engineering ». Angew. Chem ,
, , vol.127, pp.4009-4012
Genetic fusion of subunits of a dimeric protein substantially enhances its stability and rate of folding, Proc. Natl. Acad. Sci, vol.90, pp.7010-7014, 1993. ,
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev, vol.23, pp.1-25, 1997. ,
,
Combinatorial chemistry in drug discovery, Curr. Opin ,
« Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic Burkholderia ambifaria Genomic Island, Chem. Biol, vol.38, pp.117-126, 2017. ,
, Biol, vol.18, pp.665-677, 2011.
, The Crystal Structure of a Mammalian Fatty Acid
, Science, vol.321, pp.1315-1322, 2008.
« A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis, J. Antibiot, vol.70, pp.906-912, 2017. ,
,
Characterization of the 'pristinamycin supercluster ,
, Microb. Biotechnol, vol.4, pp.192-206, 2011.
,
« Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products, Proc. Natl. Acad. Sci. 1999, vol.96, pp.1846-1851 ,
,
,
,
,
,
,
,
,
,
,
,
,
« IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding », Nucleic Acids Res, vol.11, pp.329-337, 2015. ,
Rational Design and Assembly of Synthetic Trimodular Polyketide Synthases, Chem. Biol, vol.14, pp.143-151, 2007. ,
« Production of Polyunsaturated Fatty Acids by Polyketide Synthases in Both Prokaryotes and Eukaryotes, Science, vol.293, pp.290-293, 2001. ,
« Comprehensive Analysis of Distinctive Polyketide and Nonribosomal Peptide Structural Motifs Encoded in Microbial Genomes ,
, Mol. Biol, vol.368, pp.1500-1517, 2007.
,
, Domain of KirCI Loads Malonyl Extender Units to the ACPs of the Kirromycin PKS
, ChemBioChem, vol.14, pp.1343-1352, 2013.
, « Supramolecular Templating in Kirromycin Biosynthesis: The Acyltransferase KirCII Loads Ethylmalonyl-CoA Extender onto a Specific ACP of the trans-AT PKS, vol.18, pp.438-444, 2011.
, Slavcev R. « Bacteriophage recombination systems and biotechnical applications, vol.6, pp.2841-2851, 2014.
, Characterization of virginiamycin S biosynthetic genes from Streptomyces virginiae, vol.286, pp.283-290, 2002.
Natural Products as Leads to Potential Drugs: An Old Process or the New Hope for Drug Discovery?, J. Med. Chem, vol.51, pp.2589-2599, 2008. ,
, Natural Products As Sources of New Drugs over the, p.30
, , vol.75, pp.311-335, 1981.
« Exploiting the mosaic structure of transacyltransferase polyketide synthases for natural product discovery and pathway dissection ,
> Nilius A. « Ketolides: the future of the macrolides?, Curr. Opin. Pharmacol, vol.26, pp.493-500, 1997. ,
The Basics of Diversity-Oriented Synthesis, Divers. Oriented Synth ,
, , vol.8, pp.978-979, 2013.
,
« Post-PKS tailoring steps in natural productproducing actinomycetes from the perspective of combinatorial biosynthesis, Intrinsically Disordered Proteins and Intrinsically Disordered Protein Regions, vol.13, pp.553-584, 2006. ,
,
« Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners, BMC Genomics, vol.9, issue.1, p.1, 2008. ,
A hybrid modular polyketide synthase obtained by domain swapping, Chem. Biol, vol.3, pp.833-839, 1996. ,
« Expanding the Chemical Palette of Industrial Microbes: Metabolic Engineering for Type III PKS-Derived Polyketides, Nat. Biotechnol, vol.25, pp.447-453, 2007. ,
, Lasting damage to bacterial ribosomes by reversibly bound virginiamycin M. » Proc. Natl. Acad. Sci, vol.14, pp.5492-5496, 1980.
Diversity of the Burkholderia Cepacia Complex and Implications for Risk Assessment of Biological Control Strains », > Piel J. « Biosynthesis of polyketides by trans-AT polyketide synthases, vol.39, pp.4576-4581, 2001. ,
, , vol.27, pp.996-1047, 2010.
« A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles, Proc. Natl. Acad. Sci. 2002, vol.99, pp.14002-14007 ,
« Characterization of biosynthetic gene cluster for the production of virginiamycin M, a streptogramin type A antibiotic ,
Duplicated Acyl Carrier Proteins, Which Increase Polyketide Antibiotic Production, Can Apparently Function Either in Parallel or in Series, J. Biol. Chem, vol.393, pp.6399-6408, 2005. ,
Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: a route to simple statin analogues, Chem. Biol. 1999, vol.6, pp.731-741 ,
,
Model of Structure and Catalysis for Ketoreductase Domains in Modular Polyketide Synthases, Nat. Chem. Biol, vol.42, pp.75-81, 2003. ,
Engineering a polyketide with a longer chain by insertion of an extra module into the erythromycin-producing polyketide synthase, Nat. Prod. Rep, vol.19, pp.475-485, 2001. ,
, Genetics of Actinorhodin Biosynthesis by
, Streptomyces coelicolor, vol.3, issue.2, pp.35-43, 1979.
,
drug discovery, and genome mining, Appl. Microbiol. Biotechnol, vol.97, pp.969-978, 2013. ,
« Engineered biosynthesis of hybrid macrolide polyketides containing dangolosamine and d-mycaminose moieties, Org. Biomol. Chem, vol.6, p.3315, 2008. ,
Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria », Nature, vol.413, pp.814-821, 2001. ,
A Bacillus subtilis large ORF coding for a polypeptide highly similar to polyketide synthases, vol.130, pp.65-71, 1993. ,
,
« Quorum-Sensing-Regulated Bactobolin Production by Burkholderia thailandensis E264, Org. Lett, vol.12, pp.716-719, 2010. ,
« Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms, Curr. Opin. Chem. Biol, vol.7, pp.285-295, 2003. ,
,
,
, « CATH: comprehensive structural and functional annotations for genome sequences
Membrane Localization of Motility, Signaling, and Polyketide Synthetase Proteins in Myxococcus xanthus, Nucleic Acids Res, vol.43, pp.5066-5075, 2003. ,
« Catalytically Active Tetramodular 6-Deoxyerythonolide B Synthase Fusion Proteins ,
, , vol.4, pp.1225-1228, 2003.
, Evidence for a double-helical structure for modular polyketide synthases, Nat. Struct. Biol
, Polyketide biosynthesis: a millennium review, vol.3, pp.188-192
, , vol.18, pp.380-416, 2001.
Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans, Proc. Natl. Acad. Sci. U. S. A, 2004. ,
« A singular enzymatic megacomplex from Bacillus subtilis, Proc. Natl. Acad. Sci, vol.101, pp.305-310, 2007. ,
, « Identification of two polyketide synthase gene clusters on the linear plasmid pSLA2-L in Streptomyces rochei, Gene, vol.246, pp.123-131, 2000.
Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics, Diversity-oriented synthesis: exploring the intersections between chemistry and biology, vol.1, p.11 ,
« Formation of functional heterologous complexes using subunits from the picromycin, erythromycin and oleandomycin polyketide synthases ,
, Biol, vol.7, pp.77-84, 2000.
, Structural and Mechanistic Analysis of Protein Interactions in Module 3 of the 6-Deoxyerythronolide B Synthase
« The 2.7-Å crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase, Proc. Natl, vol.14, pp.931-943, 2007. ,
, Polyketide Chain Length Control by Chain Length, vol.103, pp.11124-11129, 2006.
« Analysis of Modular-iterative Mixed Biosynthesis of Lankacidin by Heterologous Expression and Gene Fusion, Extensive Mutational Analysis of Modular-Iterative Mixed Polyketide Biosynthesis of Lankacidin in Streptomyces rochei, vol.125, pp.700-708, 2003. ,
Skipping in a Hybrid Polyketide Synthase: Evidence for ACP-to-ACP Chain Transfer, PLoS Comput. Biol. 2007, vol.73, pp.781-787, 2002. ,
Progress challenges and opportunities for the re-engineering of trans-AT polyketide synthases », Biotechnol. Lett, vol.36, pp.877-888, 2014. ,
,
,
, Polyketide Biosynthesis in the Aureothin and Neoaureothin Pathways: An Evolutionary Perspective, vol.8, pp.1841-1849, 2007.
,
« Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: Versatility from a unique substrate channel ,
, Proc. Natl. Acad. Sci, vol.98, pp.14808-14813, 2001.
, Selective Protein?Protein Interactions Direct Channeling of Intermediates between Polyketide Synthase Modules
« The case for intrinsically disordered proteins playing contributory roles in molecular recognition without a stable 3D structure, Biol. Rep, vol.40, pp.2326-2331 ,
, , vol.5
The combinatorial chemistry of nature », Nature, vol.384, pp.11-13, 1996. ,
,
, Alkylquinoline Analogues with a Methyl Group at the 3 Position That Is Required for Quorum-Sensing Regulation, J. Bacteriol, vol.190, pp.5339-5352, 2008.
« Refinement of a Lowresolution Crystal Structure to Better Understand Erythromycin Interactions on Large Ribosomal Subunit, J. Biomol. Struct. Dyn, vol.26, pp.131-146, 2008. ,
,
« Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines, Curr. Opin. Chem. Biol, 2001. ,
, , vol.5, pp.525-534
Prospects for new antibiotics: a molecule-centered perspective, J. Antibiot, vol.67, pp.7-22, 2014. ,
« How many antibiotics are produced by the genus Streptomyces ?, Arch. Microbiol, vol.176, pp.386-390, 2001. ,
« Molecular Analysis of the Kirromycin Biosynthetic Gene Cluster Revealed ?-Alanine as Precursor of the Pyridone Moiety, Methods Enzymol, vol.15, pp.3-16, 2008. ,
, The structural biology of biosynthetic megaenzymes
URL : https://hal.archives-ouvertes.fr/hal-01474060
Genetic engineering of modular PKSs: from combinatorial biosynthesis to synthetic biology, Nat. Prod. Rep, vol.11, pp.203-230, 2015. ,
Mutasynthesis -uniting chemistry and genetics for drug discovery ,
, > Weissman K. J. « Uncovering the structures of modular polyketide synthases, Trends Biotechnol, vol.25, pp.139-142, 2007.
, , vol.34, p.1035, 2017.
, The Structural Basis for Docking in Modular Polyketide, vol.7, pp.1334-1342, 2006.
, Combinatorial biosynthesis of reduced polyketides, vol.7, pp.485-494, 2006.
, Nat. Rev. Microbiol, vol.3, pp.925-936, 2005.
« Structural rearrangements of a polyketide synthase module during its catalytic cycle », Nature, vol.510, pp.560-564, 2014. ,
Intrinsically disordered proteins: administration not executive, Cyanobacterial Polyketide Synthase Docking Domains: A Tool for Engineering Natural Product Biosynthesis, vol.20, pp.945-949, 2012. ,
« Recent advances in engineering nonribosomal peptide assembly lines, Protein?Protein Recognition between Acyltransferases and Acyl Carrier Proteins in Multimodular Polyketide Synthases, vol.33, pp.317-347, 2016. ,
, Biochemistry, vol.49, pp.95-102, 2010.
, Biocatalytic asymmetric Mannich reaction of ketimines using wheat germ lipase, 2016.
, Structure and Mechanism of the trans-Acting Acyltransferase from the Disorazole Synthase, vol.6, pp.3963-3970
, , vol.50, pp.6539-6548
, Donor Acyl Carrier Proteins, Acceptor Ketosynthases, and Linker Regions to Intermodular Transfer of Intermediates in Hybrid Polyketide Synthases, Biochemistry, 2002.
« Assessing the balance between proteinprotein interactions and enzyme-substrate interactions in the channeling of intermediates between polyketide synthase modules, J. Am. Chem. Soc, vol.41, pp.6465-6474, 2001. ,
« Identification of tailoring genes involved in the modification of the polyketide backbone of rifamycin B by Amycolatopsis mediterranei S699 ». Microbiology ,
, , vol.151, pp.2515-2528
« Gamma-Butyrolactone-Dependent Expression of the Streptomyces Antibiotic Regulatory Protein Gene srrY Plays a Central Role in the Regulatory Cascade Leading to Lankacidin and Lankamycin Production in Streptomyces rochei, Proc. Natl. Acad. Sci, vol.111, pp.1308-1316, 2008. ,
,
, « Structural and biochemical characterization of the plant type III polyketide synthases of the liverwort Marchantia paleacea, vol.125, pp.95-105, 2018.
, « Portability and Structure of the Four-Helix Bundle Docking Domains of trans
« Aromatic Polyketides Produced by Bacterial Iterative Type I Polyketide Synthases, Acyltransferase Modular Polyketide Synthases, vol.11, pp.1439-1447, 2013. ,
« Divergence of multimodular polyketide synthases revealed by a didomain structure », Nat. Chem. Biol, vol.8, pp.615-621, 2012. ,
, Ces petits éléments structuraux, situés aux extrémités C-et N-terminales des sous-unités de PKS, sont responsables de leur bon appariement et donc du transfert correct de l'intermédiaire polycétidique. Pour approfondir nos connaissances sur les DD, nous avons étudié plusieurs interfaces entre sous-unités de PKS trans-AT et cis-AT. Ces travaux ont notamment conduit à l'identification de la première classe de DD chez les PKS trans-AT, et nous avons pu caractériser une interface complète, formée entre deux sous-unités consécutives au sein de la PKS virginiamycine. De plus, nous avons montré qu'au moins un des DD de paires appariées est souvent une région intrinsèquement désordonnée (IDR), ce mode de reconnaissance permet d'assurer une interaction spécifique couplée à une affinité moyenne. En effet, chez l'enacyloxine synthase, une PKS hybride cis-AT/trans-AT, les six interfaces de docking sont médiées par une IDR C-terminal. En outre, nous avons démontré que ce système présentait plusieurs classes structurales de DD, mais que des variations du code électrostatique au sein d'une classe individuelle pouvaient également être utilisées pour garantir la spécificité. Ensemble, ces résultats fournissent des indications importantes pour les futures tentatives d'utilisation des DD en ingénierie des sous-unités de PKS. Une autre stratégie innovante permettant d'obtenir de nouveaux dérivés polycétidiques, consiste à utiliser des enzymes post-PKS. Ces dernières modifient de manière extensive l'intermédiaire et lui confèrent bien souvent son activité biologique. Dans ce contexte, nous avons étudié LkcE, une enzyme bi-fonctionnelle qui catalyse une réaction rare d'oxydation d'amide, suivie d'une réaction de Mannich intramoléculaire. Nous avons résolu quatre structures cristallographiques de l'enzyme et ces données couplées aux études cinétiques, nous ont permis de proposer un mécanisme catalytique détaillé pour LkcE, > Les polycétides sont des métabolites secondaires produits par divers organismes et présentant un large spectre d'activité thérapeutique. L'organisation modulaire des enzymes responsables de leur synthèse, les polycétides synthases (PKS), en font des cibles attrayantes pour la biologie synthétique visant l'obtention de nouvelles structures de polycétides. L'une des stratégies les plus prometteuses à ce jour consiste à échanger des sous-unités entières entre différents systèmes PKS
One of the most promising strategies to date consists in swapping of whole sub-units between different PKS systems. However, the success of this strategy critically depends on understanding and exploiting 'docking domains' -the protein sequences at the C-and N-terminal extremities of the subunits which are responsible for correctly ordering the polypeptides, and therefore for faithful chain transfer. To increase our knowledge of DDs, we investigated several interfaces in both trans-AT and cis-AT PKSs. This work led notably to the identification of the first family of DDs from trans-AT PKSs, and we were further able to characterize a complete interface formed between two consecutive subunits within the virginiamycin PKS. In addition, we showed that at least one DD of matched pairs is often an intrinsically disordered region (IDR), as this type of interaction motif allows for specific but medium affinity contacts. Indeed, in the enacyloxin hybrid cis-AT/trans-AT PKS which we also investigated extensively, docking at every interface is mediated by a C-terminal IDR. In addition, we demonstrated that multiple structural classes of DD are present within the system, but that variations of the electrostatic 'code' within an individual structural class can also be used to ensure specificity. Taken together, these results provide important guidelines for future attempts to deploy DDs in subunit engineering. Another attractive target for synthetic biology are the so-called 'post-PKS' enzymes, which chemically decorate the initially-formed structure, and are often essential for their bioactivity. In this context, we studied LkcE, a bi-functional enzyme that catalyzes a rare amide oxidation followed by an intramolecular Mannich reaction to yield the lankacidin macrocycle -both to understand its unusual mechanism and to evaluate its suitability as a general polyketide modifying enzyme. We solved four crystal structures of the enzyme, Complex polyketides are secondary metabolites which are produced by a range of different organisms, and which present a broad spectrum of therapeutic activity. The modular organization of the enzymes responsible for their synthesis, the polyketide synthases (PKS), makes them attractive targets for synthetic biology aimed at obtaining new polyketide structures ,
, Moreover, we showed that LkcE displays a certain tolerance toward its substrate structures, suggesting its usefulness as a general catalyst for cyclisation/ligation reaction in synthetic biology and chemical synthesis. Key words: polyketide, polyketide synthases, docking domains