A Family of Pyrazinone Natural Products from a Conserved Nonribosomal Peptide Synthetase in Staphylococcus aureus Michael Zimmermann, Michael A. Fischbach

Slides:

Advertisements

Similar presentations

Halogen Bonds Form the Basis for Selective P-TEFb Inhibition by DRB Sonja Baumli, Jane A. Endicott, Louise N. Johnson Chemistry & Biology Volume 17, Issue.

Advertisements

Proteasome Inhibition by Fellutamide B Induces Nerve Growth Factor Synthesis John Hines, Michael Groll, Margaret Fahnestock, Craig M. Crews Chemistry &

Glycosidase Inhibition by Macrolide Antibiotics Elucidated by STD-NMR Spectroscopy Ali Sadeghi-Khomami, Michael D. Lumsden, David L. Jakeman Chemistry.

Sweetly Expanding Enzymatic Glycodiversification

Volume 22, Issue 5, Pages v-vi (May 2015)

Now Playing: Farnesol in the Biofilm

Tailor-Made Peptide Synthetases

Volume 19, Issue 9, Pages (September 2012)

“Seeing” the Invisibles at the Single-Molecule Level

Genome Evolution: Horizontal Movements in the Fungi

Biosynthesis of the Antitumor Agent Chartreusin Involves the Oxidative Rearrangement of an Anthracyclic Polyketide Zhongli Xu, Kathrin Jakobi, Katrin.

Volume 20, Issue 10, Pages (October 2013)

Genomic Mining for Aspergillus Natural Products

Volume 15, Issue 2, Pages (February 2008)

Adding Specificity to Artificial Transcription Activators

Finding the Missing Code of RNA Recognition by PUF Proteins

Genome Evolution: Horizontal Movements in the Fungi

Volume 13, Issue 4, Pages (April 2006)

Volume 17, Issue 2, Pages (February 2010)

Volume 20, Issue 8, Pages (August 2013)

Volume 14, Issue 1, Pages (January 2007)

Volume 15, Issue 9, Pages (September 2008)

An FAD-Dependent Pyridine Nucleotide-Disulfide Oxidoreductase Is Involved in Disulfide Bond Formation in FK228 Anticancer Depsipeptide Cheng Wang, Shane.

Biosynthesis of Actinorhodin and Related Antibiotics: Discovery of Alternative Routes for Quinone Formation Encoded in the act Gene Cluster Susumu Okamoto,

Volume 20, Issue 8, Pages (August 2013)

Jeremy J. Minty, S. Marjan Varedi K, Xiaoxia Nina Lin

Targeting the Undruggable Proteome: The Small Molecules of My Dreams

Benjamin N. Mijts, Pyung Cheon Lee, Claudia Schmidt-Dannert

Volume 17, Issue 10, Pages (October 2010)

Volume 19, Issue 2, Pages (February 2012)

Volume 22, Issue 4, Pages (April 2015)

Volume 14, Issue 5, Pages (May 2007)

Lessons from the Past and Charting the Future of Marine Natural Products Drug Discovery and Chemical Biology William H. Gerwick, Bradley S. Moore Chemistry.

Jekyll & Hyde: Evolution of a Superfamily

No Need To Be Pure: Mix the Cultures!

Kevin J. Forsberg, Sanket Patel, Timothy A. Wencewicz, Gautam Dantas

Volume 19, Issue 3, Pages (March 2012)

Yit-Heng Chooi, Ralph Cacho, Yi Tang Chemistry & Biology

Volume 14, Issue 8, Pages (August 2007)

Andy Weiss, Renee M. Fleeman, Lindsey N. Shaw Cell Chemical Biology

Johnson Cheung, Michael E.P. Murphy, David E. Heinrichs

Now Playing: Farnesol in the Biofilm

In Vivo Biocombinatorial Synthesis of Lipopeptides by COM Domain-Mediated Reprogramming of the Surfactin Biosynthetic Complex Claudia Chiocchini, Uwe.

Staphylococcus aureus and Bacillus subtilis W23 Make Polyribitol Wall Teichoic Acids Using Different Enzymatic Pathways Stephanie Brown, Timothy Meredith,

Volume 21, Issue 8, Pages v-vi (August 2014)

Volume 11, Issue 7, Pages (July 2004)

In Vivo Characterization of Nonribosomal Peptide Synthetases NocA and NocB in the Biosynthesis of Nocardicin A Jeanne M. Davidsen, Craig A. Townsend

Toward the Pathway of S. aureus WTA Biosynthesis

Volume 17, Issue 4, Pages (April 2010)

Volume 15, Issue 8, Pages (August 2008)

Markerless Mutations in the Myxothiazol Biosynthetic Gene Cluster

Volume 18, Issue 4, Pages (April 2011)

Volume 18, Issue 12, Pages (December 2011)

Volume 18, Issue 11, Pages (November 2011)

Screening for a Diamond in the Rough

Volume 17, Issue 3, Pages (March 2010)

Volume 10, Issue 4, Pages (April 2003)

L-DOPA Ropes in tRNAPhe

Volume 11, Issue 4, Pages (April 2004)

Harnessing the Antioxidant Power with ARE-Inducing Compounds

Volume 21, Issue 9, Pages (September 2014)

Volume 21, Issue 7, Pages (July 2014)

Flexing and Stretching in Nonribosomal Peptide Synthetases

Volume 13, Issue 6, Pages (June 2006)

Volume 12, Issue 3, Pages (March 2005)

A One-Pot Chemoenzymatic Synthesis for the Universal Precursor of Antidiabetes and Antiviral Bis-Indolylquinones Patrick Schneider, Monika Weber, Karen.

Volume 21, Issue 9, Pages (September 2014)

Volume 13, Issue 11, Pages (November 2006)

Strategies for Engineering Natural Product Biosynthesis in Fungi

Volume 18, Issue 3, Pages (March 2011)

Presentation transcript:

A Family of Pyrazinone Natural Products from a Conserved Nonribosomal Peptide Synthetase in Staphylococcus aureus Michael Zimmermann, Michael A. Fischbach Chemistry & Biology Volume 17, Issue 9, Pages 925-930 (September 2010) DOI: 10.1016/j.chembiol.2010.08.006 Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 1 Schematic of the S. aureus Pyrazinone (pzn) Gene Cluster and Proposed Biosynthetic Pathway for the Staphylococcus Pyrazinones A: adenylation domain; C: condensation domain; T: thiolation domain; R: reductase domain. Chemistry & Biology 2010 17, 925-930DOI: (10.1016/j.chembiol.2010.08.006) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 2 Strategy for the Allelic Replacement of pznA in S. aureus RN4220 After integration of the plasmid by the first genomic crossover event, the second crossover can either lead to the desired knockout strain or reversion to the wild-type strain. Successful allelic replacement is demonstrated by Southern blot. Wt corresponds to the wild-type strain of S. aureus RN4220. Ko#1 and #2 correspond to independently generated and selected knockout strains for the NRPS gene pznA. Scheme adapted from Horsburgh et al. (1999). Chemistry & Biology 2010 17, 925-930DOI: (10.1016/j.chembiol.2010.08.006) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 3 Comparison of Pyrazinone Production across Staphylococcus Species RP-HPLC analysis (325 nm) of methanol extracts of culture supernatants after 48 hr are shown. RN42220ko corresponds to the ΔpznA S. aureus strain. Both S. epidermidis strains harbor the pzn gene cluster, whereas S. saprophyticus S-41 does not. Inset A: Time course for the production of phevalin by S. aureus RN4220wt. Inset B: Ultraviolet/visible absorption spectrum of phevalin. Chemistry & Biology 2010 17, 925-930DOI: (10.1016/j.chembiol.2010.08.006) Copyright © 2010 Elsevier Ltd Terms and Conditions