Volume 23, Issue 4, Pages (April 2016)

Slides:



Advertisements
Similar presentations
Debosmita Sardar, Zhenjian Lin, Eric W. Schmidt  Chemistry & Biology 
Advertisements

Volume 13, Issue 6, Pages (June 2006)
Metagenomic Approaches for Exploiting Uncultivated Bacteria as a Resource for Novel Biosynthetic Enzymology  Micheal C. Wilson, Jörn Piel  Chemistry &
Volume 22, Issue 5, Pages v-vi (May 2015)
Enzyme Annotation with Chemical Tools
Volume 23, Issue 8, Pages (August 2016)
Volume 19, Issue 9, Pages (September 2012)
Foundations for Directed Alkaloid Biosynthesis
Miglena Manandhar, John E. Cronan  Chemistry & Biology 
Nature’s Strategy for Catalyzing Diels-Alder Reaction
News in Ubiquinone Biosynthesis
Volume 20, Issue 6, Pages (June 2013)
Volume 13, Issue 4, Pages (April 2006)
Mechanism of Thioesterase-Catalyzed Chain Release in the Biosynthesis of the Polyether Antibiotic Nanchangmycin  Tiangang Liu, Xin Lin, Xiufen Zhou, Zixin.
Biosynthesis of Actinorhodin and Related Antibiotics: Discovery of Alternative Routes for Quinone Formation Encoded in the act Gene Cluster  Susumu Okamoto,
Volume 18, Issue 9, Pages (September 2011)
Volume 13, Issue 11, Pages (November 2006)
Volume 19, Issue 2, Pages (February 2012)
A Revised Pathway Proposed for Staphylococcus aureus Wall Teichoic Acid Biosynthesis Based on In Vitro Reconstitution of the Intracellular Steps  Stephanie.
Redesign of a Dioxygenase in Morphine Biosynthesis
Identification and Characterization of the Lysobactin Biosynthetic Gene Cluster Reveals Mechanistic Insights into an Unusual Termination Module Architecture 
Divergent Pathways in the Biosynthesis of Bisindole Natural Products
Kento Koketsu, Hiroki Oguri, Kenji Watanabe, Hideaki Oikawa 
Characterization of a Fungal Thioesterase Having Claisen Cyclase and Deacetylase Activities in Melanin Biosynthesis  Anna L. Vagstad, Eric A. Hill, Jason W.
Elucidation of the Biosynthetic Gene Cluster and the Post-PKS Modification Mechanism for Fostriecin in Streptomyces pulveraceus  Rixiang Kong, Xuejiao.
Volume 22, Issue 2, Pages (February 2015)
Volume 22, Issue 10, Pages (October 2015)
Yit-Heng Chooi, Ralph Cacho, Yi Tang  Chemistry & Biology 
Insights into the Generation of Structural Diversity in a tRNA-Dependent Pathway for Highly Modified Bioactive Cyclic Dipeptides  Tobias W. Giessen, Alexander M.
Yihan Wu, Mohammad R. Seyedsayamdost  Cell Chemical Biology 
Volume 24, Issue 6, Pages e7 (June 2017)
Volume 20, Issue 12, Pages (December 2013)
Volume 19, Issue 5, Pages (May 2012)
Yi-Ling Du, Doralyn S. Dalisay, Raymond J. Andersen, Katherine S. Ryan 
Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation  Wei Ding, Chun.
Andy Weiss, Renee M. Fleeman, Lindsey N. Shaw  Cell Chemical Biology 
Volume 21, Issue 3, Pages (March 2014)
PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the Biosynthesis of Alkylquinolone Signaling Molecules  Steffen Lorenz Drees,
Functional and Structural Analysis of Programmed C-Methylation in the Biosynthesis of the Fungal Polyketide Citrinin  Philip A. Storm, Dominik A. Herbst,
Volume 20, Issue 4, Pages (April 2013)
Volume 17, Issue 1, Pages (January 2010)
Volume 17, Issue 4, Pages (April 2010)
Volume 22, Issue 10, Pages (October 2015)
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 20, Issue 4, Pages (April 2013)
Volume 16, Issue 6, Pages (June 2009)
One Enzyme, Three Metabolites: Shewanella algae Controls Siderophore Production via the Cellular Substrate Pool  Sina Rütschlin, Sandra Gunesch, Thomas.
Volume 22, Issue 6, Pages (June 2015)
Volume 16, Issue 4, Pages (April 2009)
Elegant Metabolite Biosynthesis
Volume 15, Issue 2, Pages (February 2008)
Characterization of the Biosynthetic Gene Cluster for Benzoxazole Antibiotics A33853 Reveals Unusual Assembly Logic  Meinan Lv, Junfeng Zhao, Zixin Deng,
Gerald Lackner, Markus Bohnert, Jonas Wick, Dirk Hoffmeister 
Volume 15, Issue 8, Pages (August 2008)
Volume 24, Issue 2, Pages (February 2017)
Nature’s Strategy for Catalyzing Diels-Alder Reaction
Biosynthetic Pathway Connects Cryptic Ribosomally Synthesized Posttranslationally Modified Peptide Genes with Pyrroloquinoline Alkaloids  Peter A. Jordan,
Aza-Tryptamine Substrates in Monoterpene Indole Alkaloid Biosynthesis
Volume 15, Issue 9, Pages (September 2008)
Volume 13, Issue 4, Pages (April 2006)
Dual Carbamoylations on the Polyketide and Glycosyl Moiety by Asm21 Result in Extended Ansamitocin Biosynthesis  Yan Li, Peiji Zhao, Qianjin Kang, Juan.
Volume 19, Issue 3, Pages (March 2012)
Volume 18, Issue 8, Pages (August 2011)
Volume 17, Issue 5, Pages (May 2010)
Debosmita Sardar, Zhenjian Lin, Eric W. Schmidt  Chemistry & Biology 
Volume 21, Issue 3, Pages (March 2014)
Volume 12, Issue 10, Pages (October 2005)
Volume 22, Issue 6, Pages (June 2015)
Volume 22, Issue 4, Pages vii-viii (April 2015)
Presentation transcript:

Volume 23, Issue 4, Pages 508-516 (April 2016) A Multifunctional Monooxygenase XanO4 Catalyzes Xanthone Formation in Xantholipin Biosynthesis via a Cryptic Demethoxylation  Lingxin Kong, Weike Zhang, Yit Heng Chooi, Lu Wang, Bo Cao, Zixin Deng, Yiwen Chu, Delin You  Cell Chemical Biology  Volume 23, Issue 4, Pages 508-516 (April 2016) DOI: 10.1016/j.chembiol.2016.03.013 Copyright © 2016 Elsevier Ltd Terms and Conditions

Cell Chemical Biology 2016 23, 508-516DOI: (10. 1016/j. chembiol. 2016 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Chemical Structures and Biosynthetic Routes (A) Structures of other natural polycylic xanthone antibiotics. (B) The proposed biosynthetic pathway of the xanthone ring in xantholipin. The xanthone ring is shown in red with the oxygen atom originating in the xanthone ring marked in blue. For related polycyclic xanthone antibiotics, see Figure S1. Cell Chemical Biology 2016 23, 508-516DOI: (10.1016/j.chembiol.2016.03.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 2 In Vitro Reconstitution of the Xanthone Ring Catalyzed by XanO4 (A) HPLC profiles of (i) XanO4 incubated with 2; (ii) Arx30 incubated with 2; (iii) standard 3; (iv) standard 2. (B) Time course of production of 3 catalyzed by XanO4. 20 μM XanO4 was incubated with 50 μM compound 2 for (i) 0.5 min; (ii) 1 min; (iii) 1.5 min; (iv) 2 min; (v) 3 min; (vi) 5 min. Enzymatic characterization of XanO4 is shown in Figure S2; mass and high-resolution electrospray ionization-MS analyses are given in Figure S3. Cell Chemical Biology 2016 23, 508-516DOI: (10.1016/j.chembiol.2016.03.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 3 XanO4 Catalyzes Xanthone Ring Assembly Coupled with Demethoxylation (A) HPLC profiles of reactions of XanO4 with compound 2 (i) under 18O2; (ii) under 16O2; (iii) standard 2. (B) MS analysis and the proposed chemical molecular structures of the products in (i) reactions with 18O2; (ii) reactions with 16O2. Oxygen atoms derived from 18O2 and 16O2 are marked with * and #, respectively. Cell Chemical Biology 2016 23, 508-516DOI: (10.1016/j.chembiol.2016.03.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 4 Cryptic Demethoxylation and Remethylation Involved in Xantholipin Biosynthesis (A) Time course of production of 4 catalyzed by XanO4R45A. 20 μM XanO4R45A was incubated with 50 μM compound 2 for (i) 30 min; (ii) 2 hr; (iii) 6 hr; (iv) 10 hr; (v) overnight; with standard 2 as control (vi). (B) MS analysis of the product from 2 catalyzed by XanO4R45A (i) under 16O2; (ii) under 18O2; with standard 2 as control (iii). Oxygen atoms derived from 18O2 and 16O2 are marked with * and #, respectively. (C) HPLC profiles of reactions of (i) compound 4 with XanO4; (ii) compound 4 with XanM3; (iii) compound 3 with XanM3; (iv) compound 4 with XanO4 and XanM3; (v) compound 2 with XanO4 and XanM3; (vi) standard 5; (vii) standard 4; (viii) standard 3; (ix) standard 2. Cell Chemical Biology 2016 23, 508-516DOI: (10.1016/j.chembiol.2016.03.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 5 Phylogenetic Analysis of XanO4 with Other Known BVMOs The neighbor-joining phylogenetic tree was constructed by using MEGA V5.10 with 500 bootstrap replicates. The scale 0.2 is the genetic distance. Cell Chemical Biology 2016 23, 508-516DOI: (10.1016/j.chembiol.2016.03.013) Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 6 Proposed Enzymatic Mechanisms for XanO4 Red atoms are derived from substrate 2 while blue atoms arise from an oxygen molecule. The green methyl group was disposed from 2 in the form of methanol. The first oxygen insertion catalyzed by XanO4 was proposed to proceed through the attack of activated FAD-O-O− on carbon atom C17, leading to the formation of a possible anthraquinone epoxide intermediate between carbon C16 and C17. The formation of this anthraquinone epoxide intermediate may facilitate the next nucleophilic attack of FAD-O-O− on carbonyl carbon atom C15 (in pathway I). Following the classic BV oxidation procedure, the migratory rearrangement led to the formation of a lactone epoxide intermediate. The hydrolysis of lactone initiated the construction of the xanthone ring, opening of the epoxy ring, oxidative decarboxylation, and simultaneous removal of the methoxy group on C17 in the form of methanol. In pathway II, XanO4R45A abolished catalysis of BV oxidation of C15, and somehow produced only demethoxylated anthraquinone 4 via opening of the epoxy ring. The presence of a methoxy group at C17 in 4 prevented the formation of epoxide or recognition by XanO4, so compound 4 existed as a shunt product in the xantholipin biosynthesis pathway. Cell Chemical Biology 2016 23, 508-516DOI: (10.1016/j.chembiol.2016.03.013) Copyright © 2016 Elsevier Ltd Terms and Conditions