Volume 21, Issue 11, Pages (November 2014)

Slides:

Advertisements

Similar presentations

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

Advertisements

Structure-Based Engineering of Angucyclinone 6-Ketoreductases

Volume 16, Issue 10, Pages (October 2009)

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

Now Playing: Farnesol in the Biofilm

Katharina M. Hoyer, Christoph Mahlert, Mohamed A. Marahiel

Cross-Catalytic Replication of an RNA Ligase Ribozyme

Antibiotics: A New Hope

Foundations for Directed Alkaloid Biosynthesis

Miglena Manandhar, John E. Cronan Chemistry & Biology

Volume 21, Issue 8, Pages (August 2014)

Nature’s Strategy for Catalyzing Diels-Alder Reaction

Volume 15, Issue 5, Pages (May 2008)

Adding Specificity to Artificial Transcription Activators

News in Ubiquinone Biosynthesis

Peter Bernhardt, Elizabeth McCoy, Sarah E. O'Connor

Volume 13, Issue 11, Pages (November 2006)

Volume 17, Issue 10, Pages (October 2010)

Volume 11, Issue 9, Pages (September 2004)

Volume 23, Issue 4, Pages (April 2016)

Volume 20, Issue 3, Pages (March 2013)

Highly Efficient Self-Replicating RNA Enzymes

Volume 3, Issue 5, Pages (November 2017)

Combinatorial Enzymatic Synthesis of Heparan Sulfate

Redesign of a Dioxygenase in Morphine Biosynthesis

No Need To Be Pure: Mix the Cultures!

Kento Koketsu, Hiroki Oguri, Kenji Watanabe, Hideaki Oikawa

Volume 13, Issue 4, Pages (April 2006)

Volume 22, Issue 10, Pages (October 2015)

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

Volume 21, Issue 5, Pages (May 2014)

Volume 19, Issue 5, Pages (May 2012)

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

Volume 15, Issue 7, Pages (July 2008)

PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the Biosynthesis of Alkylquinolone Signaling Molecules Steffen Lorenz Drees,

Now Playing: Farnesol in the Biofilm

Macrophage Activation: On PAR with LPS

A Subdomain Swap Strategy for Reengineering Nonribosomal Peptides

Volume 15, Issue 4, Pages (April 2008)

Volume 21, Issue 11, Pages (November 2014)

Volume 22, Issue 10, Pages (October 2015)

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

An Artificial Pathway to 3,4-Dihydroxybenzoic Acid Allows Generation of New Aminocoumarin Antibiotic Recognized by Catechol Transporters of E. coli Silke.

Volume 12, Issue 11, Pages (November 2005)

Tandem Enzymatic Oxygenations in Biosynthesis of Epoxyquinone Pharmacophore of Manumycin-type Metabolites Zhe Rui, Moriah Sandy, Brian Jung, Wenjun Zhang

Foundations for Directed Alkaloid Biosynthesis

Volume 21, Issue 6, Pages (June 2014)

Volume 16, Issue 10, Pages (October 2009)

Volume 14, Issue 4, Pages (April 2007)

An Electrophoretic Mobility Shift Assay Identifies a Mechanistically Unique Inhibitor of Protein Sumoylation Yeong Sang Kim, Katelyn Nagy, Samantha Keyser,

Elegant Metabolite Biosynthesis

Breaking Down Order to Keep Cells Tidy

Volume 22, Issue 3, Pages (March 2015)

Structure-Based Engineering of Angucyclinone 6-Ketoreductases

Volume 13, Issue 3, Pages (March 2006)

Volume 11, Issue 9, Pages (September 2004)

Volume 22, Issue 8, Pages (August 2015)

Nature’s Strategy for Catalyzing Diels-Alder Reaction

L-DOPA Ropes in tRNAPhe

Volume 7, Issue 6, Pages R147-R151 (June 2000)

Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis

Modeling of the RAG Reaction Mechanism

Volume 21, Issue 9, Pages (September 2014)

Tools to Tackle Protein Acetylation

Volume 3, Issue 1, Pages 8-10 (July 2017)

Volume 15, Issue 6, Pages (June 2008)

Volume 22, Issue 12, Pages (December 2015)

Structure-Based Engineering of Angucyclinone 6-Ketoreductases

Volume 21, Issue 9, Pages (September 2014)

Volume 22, Issue 4, Pages vii-viii (April 2015)

Presentation transcript:

Volume 21, Issue 11, Pages 1452-1456 (November 2014) Conversion of Substrate Analogs Suggests a Michael Cyclization in Iridoid Biosynthesis Stephanie Lindner, Fernando Geu-Flores, Stefan Bräse, Nathaniel H. Sherden, Sarah E. O’Connor Chemistry & Biology Volume 21, Issue 11, Pages 1452-1456 (November 2014) DOI: 10.1016/j.chembiol.2014.09.010 Copyright © 2014 The Authors Terms and Conditions

Chemistry & Biology 2014 21, 1452-1456DOI: (10. 1016/j. chembiol. 2014 Copyright © 2014 The Authors Terms and Conditions

Figure 1 Terpene Cyclization (A) Representative canonical terpene cyclization mechanism. (B) Iridoid synthase uses 8-oxogeranial (2) as a substrate. A hydride from NADPH reduces the substrate to an enol or enolate 3, which can then cyclize to 1a. Two possible cyclization mechanisms are possible for iridoid synthase: a concerted hetero Diels-Alder (red arrows) and a stepwise Michael addition (blue arrows). Chemistry & Biology 2014 21, 1452-1456DOI: (10.1016/j.chembiol.2014.09.010) Copyright © 2014 The Authors Terms and Conditions

Figure 2 Substrate Analogs (A) Compound 5 is poised to undergo a Diels-Alder reaction (red arrows) upon enol (or enolate) formation, while the Michael reaction is disfavored. (B) Compound 6 is predisposed to undergo a Michael reaction (blue arrows) and is unlikely to undergo the Diels-Alder related Halo-Alder-ene pericyclic reaction. Disfavored mechanisms are shown in gray. Compounds 7 and 10 are shown in enol forms. Enzymatic products that were isolated are shown in red, along with corresponding kcat and KM values. Chemistry & Biology 2014 21, 1452-1456DOI: (10.1016/j.chembiol.2014.09.010) Copyright © 2014 The Authors Terms and Conditions

Figure 3 Synthetic Procedures for Compounds 5 and 6 (A) p-Toluenesulfonic acid monohydrate, 2,2-dimethylpropane-1,3-diol, benzene, 110°C, 2 hr (quant.) (B) SeO2, Na2SO4, dichloromethane, reaction time (r.t.), 2 d (11%). (C) Sodium chlorodifluoroacetate, PPh3, dimethylformamide, 100°C, 3 hr (18%). (D) HCl, THF, r.t., 1 hr (71%). (E) NaBH4, MeOH, 0°C-r.t., 1.5 hr (36%). (F) Tosyl chloride, 4-dimethylaminopyridine, NEt3, dichloromethane, r.t., 3 hr (45%). (G) Trifluoroacetic acid/H2O (1:1), dichloromethane, r.t., 10 min (69%). Full details are provided in the Supplemental Information. Chemistry & Biology 2014 21, 1452-1456DOI: (10.1016/j.chembiol.2014.09.010) Copyright © 2014 The Authors Terms and Conditions