C-S Bond Cleavage by a Polyketide Synthase Domain
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Differentiating Two Closely Related Alexandrium Species Using Comparative Quantitative Proteomics
toxins Article Differentiating Two Closely Related Alexandrium Species Using Comparative Quantitative Proteomics Bryan John J. Subong 1,2,* , Arturo O. Lluisma 1, Rhodora V. Azanza 1 and Lilibeth A. Salvador-Reyes 1,* 1 Marine Science Institute, University of the Philippines- Diliman, Velasquez Street, Quezon City 1101, Philippines; [email protected] (A.O.L.); [email protected] (R.V.A.) 2 Department of Chemistry, The University of Tokyo, 7-3-1 Hongo, Bunkyo City, Tokyo 113-8654, Japan * Correspondence: [email protected] (B.J.J.S.); [email protected] (L.A.S.-R.) Abstract: Alexandrium minutum and Alexandrium tamutum are two closely related harmful algal bloom (HAB)-causing species with different toxicity. Using isobaric tags for relative and absolute quantita- tion (iTRAQ)-based quantitative proteomics and two-dimensional differential gel electrophoresis (2D-DIGE), a comprehensive characterization of the proteomes of A. minutum and A. tamutum was performed to identify the cellular and molecular underpinnings for the dissimilarity between these two species. A total of 1436 proteins and 420 protein spots were identified using iTRAQ-based proteomics and 2D-DIGE, respectively. Both methods revealed little difference (10–12%) between the proteomes of A. minutum and A. tamutum, highlighting that these organisms follow similar cellular and biological processes at the exponential stage. Toxin biosynthetic enzymes were present in both organisms. However, the gonyautoxin-producing A. minutum showed higher levels of osmotic growth proteins, Zn-dependent alcohol dehydrogenase and type-I polyketide synthase compared to the non-toxic A. tamutum. Further, A. tamutum had increased S-adenosylmethionine transferase that may potentially have a negative feedback mechanism to toxin biosynthesis. -
N-Carbamoylation of 2,4-Diaminobutyrate Reroutes the Outcome in Padanamide Biosynthesis
Chemistry & Biology Article N-Carbamoylation of 2,4-Diaminobutyrate Reroutes the Outcome in Padanamide Biosynthesis Yi-Ling Du,1 Doralyn S. Dalisay,1 Raymond J. Andersen,1,2 and Katherine S. Ryan1,* 1Department of Chemistry 2Department of Earth, Ocean and Atmospheric Sciences University of British Columbia, Vancouver, BC V6T 1Z1, Canada *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chembiol.2013.06.013 SUMMARY literature. It is interesting that a compound identical to padana- mide A, named actinoramide A (Nam et al., 2011), was indepen- Padanamides are linear tetrapeptides notable for the dently reported from Streptomyces sp. CNQ-027. This actinomy- absence of proteinogenic amino acids in their struc- cete strain was isolated from sediment on the opposite side of the tures. In particular, two unusual heterocycles, (S)- Pacific Ocean, near San Diego, CA, suggesting a potentially wide 3-amino-2-oxopyrrolidine-1-carboxamide (S-Aopc) distribution of the padanamides/actinoramides. It is intriguing and (S)-3-aminopiperidine-2,6-dione (S-Apd), are that, whereas padanamide A and actinoramide A are identical, found at the C-termini of padanamides A and B, the minor compounds (actinoramides B and C) co-isolated from Streptomyces sp. CNQ-027 are unique (Figure 1A). Total respectively. Here we identify the padanamide synthesis of padanamides A and B was recently reported (Long biosynthetic gene cluster and carry out systematic et al., 2013), confirming the previous structural elucidations. gene inactivation studies. Our results show that The padanamides attracted our attention for their many padanamides are synthesized by highly dissociated unusual chemical features. -
Polyketide Biosynthesis Beyond the Type I, II and III Polyketide Synthase Paradigms Ben Shen
285 Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms Ben Shen Recent literature on polyketide biosynthesis suggests that Three types of bacterial PKSs are known to date. First, polyketide synthases have much greater diversity in both type I PKSs are multifunctional enzymes that are orga- mechanism and structure than the current type I, II and III nized into modules, each of which harbors a set of distinct, paradigms. These examples serve as an inspiration for searching non-iteratively acting activities responsible for the cata- novel polyketide synthases to give new insights into polyketide lysis of one cycle of polyketide chain elongation, as biosynthesis and to provide new opportunities for combinatorial exemplified by the 6-deoxyerythromycin B synthase biosynthesis. (DEBS) for the biosynthesis of reduced polyketides (i.e. macrolides, polyethers and polyene) such as erythro- Addresses mycin A (1)(Figure 1a) [1]. Second, type II PKSs are Division of Pharmaceutical Sciences and Department of Chemistry, multienzyme complexes that carry a single set of iteratively University of Wisconsin, Madison, WI 53705, USA acting activities, as exemplified by the tetracenomycin e-mail: [email protected] PKS for the biosynthesis of aromatic polyketides (often polycyclic) such as tetracenomycin C (2)(Figure 1b) [2]. Current Opinion in Chemical Biology 2003, 7:285–295 Third, type III PKSs, also known as chalcone synthase- like PKSs, are homodimeric enzymes that essentially are This review comes from a themed section on iteratively acting condensing enzymes, as exemplified by Biocatalysis and biotransformation Edited by Tadhg Begley and Ming-Daw Tsai the RppA synthase for the biosynthesis of aromatic poly- ketides (often monocyclic or bicyclic), such as flavolin (3) 1367-5931/03/$ – see front matter (Figure 1c) [3]. -
Letters to Nature
letters to nature Received 7 July; accepted 21 September 1998. 26. Tronrud, D. E. Conjugate-direction minimization: an improved method for the re®nement of macromolecules. Acta Crystallogr. A 48, 912±916 (1992). 1. Dalbey, R. E., Lively, M. O., Bron, S. & van Dijl, J. M. The chemistry and enzymology of the type 1 27. Wolfe, P. B., Wickner, W. & Goodman, J. M. Sequence of the leader peptidase gene of Escherichia coli signal peptidases. Protein Sci. 6, 1129±1138 (1997). and the orientation of leader peptidase in the bacterial envelope. J. Biol. Chem. 258, 12073±12080 2. Kuo, D. W. et al. Escherichia coli leader peptidase: production of an active form lacking a requirement (1983). for detergent and development of peptide substrates. Arch. Biochem. Biophys. 303, 274±280 (1993). 28. Kraulis, P.G. Molscript: a program to produce both detailed and schematic plots of protein structures. 3. Tschantz, W. R. et al. Characterization of a soluble, catalytically active form of Escherichia coli leader J. Appl. Crystallogr. 24, 946±950 (1991). peptidase: requirement of detergent or phospholipid for optimal activity. Biochemistry 34, 3935±3941 29. Nicholls, A., Sharp, K. A. & Honig, B. Protein folding and association: insights from the interfacial and (1995). the thermodynamic properties of hydrocarbons. Proteins Struct. Funct. Genet. 11, 281±296 (1991). 4. Allsop, A. E. et al.inAnti-Infectives, Recent Advances in Chemistry and Structure-Activity Relationships 30. Meritt, E. A. & Bacon, D. J. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277, 505± (eds Bently, P. H. & O'Hanlon, P. J.) 61±72 (R. Soc. Chem., Cambridge, 1997). -
Identification and Characterization of Enzymes Involved in Post- Translational Modifications of Phycobiliproteins in the Cyanobacterium Synechocystis Sp
University of New Orleans ScholarWorks@UNO University of New Orleans Theses and Dissertations Dissertations and Theses 8-8-2007 Identification and Characterization of Enzymes Involved in Post- translational Modifications of Phycobiliproteins in the Cyanobacterium Synechocystis sp. PCC 6803 Crystal Miller University of New Orleans Follow this and additional works at: https://scholarworks.uno.edu/td Recommended Citation Miller, Crystal, "Identification and Characterization of Enzymes Involved in Post-translational Modifications of Phycobiliproteins in the Cyanobacterium Synechocystis sp. PCC 6803" (2007). University of New Orleans Theses and Dissertations. 572. https://scholarworks.uno.edu/td/572 This Thesis is protected by copyright and/or related rights. It has been brought to you by ScholarWorks@UNO with permission from the rights-holder(s). You are free to use this Thesis in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights- holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/or on the work itself. This Thesis has been accepted for inclusion in University of New Orleans Theses and Dissertations by an authorized administrator of ScholarWorks@UNO. For more information, please contact [email protected]. Identification and Characterization of Enzymes Involved in Post-translational Modifications of Phycobiliproteins in the Cyanobacterium Synechocystis sp. PCC 6803 A Thesis Submitted to the Graduate Faculty of the University of New Orleans in partial fulfillment of the requirements for degree of Master of Science in Biological Sciences by Crystal Miller B.S. University of New Orleans, 2004 August, 2007 ACKNOWLEDGMENTS I would first like to thank my fiancé, Gus Mugnier, for always being there for me and supporting me through my graduate career. -
Investigation and Engineering of Polyketide Biosynthetic Pathways
Utah State University DigitalCommons@USU All Graduate Theses and Dissertations Graduate Studies 12-2017 Investigation and Engineering of Polyketide Biosynthetic Pathways Lei Sun Utah State University Follow this and additional works at: https://digitalcommons.usu.edu/etd Part of the Biological Engineering Commons Recommended Citation Sun, Lei, "Investigation and Engineering of Polyketide Biosynthetic Pathways" (2017). All Graduate Theses and Dissertations. 6903. https://digitalcommons.usu.edu/etd/6903 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. INVESTIGATION AND ENGINEERING OF POLYKETIDE BIOSYNTHETIC PATHWAYS by Lei Sun A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSPHY in Biological Engineering Approved: ______________________ ____________________ Jixun Zhan, Ph.D. David W. Britt, Ph.D. Major Professor Committee Member ______________________ ____________________ Dong Chen, Ph.D. Jon Takemoto, Ph.D. Committee Member Committee Member ______________________ ____________________ Elizabeth Vargis, Ph.D. Mark R. McLellan, Ph.D. Committee Member Vice President for Research and Dean of the School of Graduate Studies UTAH STATE UNIVERSITY Logan, Utah 2017 ii Copyright© Lei Sun 2017 All Rights Reserved iii ABSTRACT Investigation and engineering of polyketide biosynthetic pathways by Lei Sun, Doctor of Philosophy Utah State University, 2017 Major Professor: Jixun Zhan Department: Biological Engineering Polyketides are a large family of natural products widely found in bacteria, fungi and plants, which include many clinically important drugs such as tetracycline, chromomycin, spirolaxine, endocrocin and emodin. -
Anti-CTH (Aa 250-350) Polyclonal Antibody (DPABH-26846) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
Anti-CTH (aa 250-350) polyclonal antibody (DPABH-26846) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Antigen Description Catalyzes the last step in the transsulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Immunogen Synthetic peptide conjugated to KLH derived from within residues 250 - 350 of Human Cystathionase. Isotype IgG Source/Host Rabbit Species Reactivity Human Purification Immunogen affinity purified Conjugate Unconjugated Applications WB, ICC/IF Format Liquid Size 100 μg Buffer pH: 7.40; Constituent: PBS Preservative 0.02% Sodium Azide Storage Store at 4°C short term (1-2 weeks). Aliquot and store at -20°C or -80°C. Avoid repeated freeze / thaw cycles. GENE INFORMATION Gene Name CTH cystathionase (cystathionine gamma-lyase) [ Homo sapiens ] 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved Official Symbol CTH Synonyms CTH; cystathionase (cystathionine gamma-lyase); cystathionine gamma-lyase; gamma- cystathionase; homoserine deaminase; cysteine desulfhydrase; homoserine dehydratase; -
Rewiring Yarrowia Lipolytica Toward Triacetic Acid Lactone for Materials Generation
Rewiring Yarrowia lipolytica toward triacetic acid lactone for materials generation Kelly A. Markhama,1, Claire M. Palmerb,1, Malgorzata Chwatkoa, James M. Wagnera, Clare Murraya, Sofia Vazqueza, Arvind Swaminathana, Ishani Chakravartya, Nathaniel A. Lynda, and Hal S. Alpera,b,2 aMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712; and bInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712 Edited by Sang Yup Lee, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea, and approved January 22, 2018 (received for review December 6, 2017) Polyketides represent an extremely diverse class of secondary me- or challenging syntheses, this is not an option for any larger-scale tabolites often explored for their bioactive traits. These molecules are chemistry application. also attractive building blocks for chemical catalysis and polymeriza- Here, we focus on the interesting, yet simple, polyketide, tri- tion. However, the use of polyketides in larger scale chemistry acetic acid lactone (TAL) as it is derived from two common applications is stymied by limited titers and yields from both microbial polyketide precursors, acetyl–CoA and malonyl–CoA. TAL has and chemical production. Here, we demonstrate that an oleaginous been demonstrated as a platform chemical that can be converted organism (specifically, Yarrowia lipolytica) can overcome such produc- into a variety of valuable products traditionally derived from tion limitations owing to a natural propensity for high flux through fossil fuels including sorbic acid, a common food preservative acetyl–CoA. By exploring three distinct metabolic engineering strate- with a global demand of 100,000 t (1, 15–18). -
Substrate Channeling in Proline Metabolism Benjamin W
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by DigitalCommons@University of Nebraska University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Biochemistry -- Faculty Publications Biochemistry, Department of 2012 Substrate channeling in proline metabolism Benjamin W. Arentson University of Nebraska-Lincoln, [email protected] Nikhilesh Sanyal University of Nebraska-Lincoln, [email protected] Donald F. Becker University of Nebraska-Lincoln, [email protected] Follow this and additional works at: http://digitalcommons.unl.edu/biochemfacpub Part of the Biochemistry Commons, Biotechnology Commons, and the Other Biochemistry, Biophysics, and Structural Biology Commons Arentson, Benjamin W.; Sanyal, Nikhilesh; and Becker, Donald F., "Substrate channeling in proline metabolism" (2012). Biochemistry -- Faculty Publications. 303. http://digitalcommons.unl.edu/biochemfacpub/303 This Article is brought to you for free and open access by the Biochemistry, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Biochemistry -- Faculty Publications by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. NIH Public Access Author Manuscript Front Biosci. Author manuscript; available in PMC 2013 January 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Front Biosci. ; 17: 375–388. Substrate channeling in proline metabolism Benjamin W. Arentson1, Nikhilesh Sanyal1, and Donald F. Becker1 1Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA Abstract Proline metabolism is an important pathway that has relevance in several cellular functions such as redox balance, apoptosis, and cell survival. Results from different groups have indicated that substrate channeling of proline metabolic intermediates may be a critical mechanism. -
Orphan Enzymes Could Be an Unexplored Reservoir of New Drug Targets
Drug Discovery Today Volume 11, Numbers 7/8 April 2006 REVIEWS Reviews GENE TO SCREEN Orphan enzymes could be an unexplored reservoir of new drug targets Olivier Lespinet and Bernard Labedan Institut de Ge´ne´tique et Microbiologie, CNRS UMR 8621, Universite´ Paris Sud, Baˆtiment 400, 91405 Orsay Cedex, France Despite the immense progress of genomics, and the current availability of several hundreds of thousands of amino acid sequences, >39% of well-defined enzyme activities (as represented by enzyme commission, EC, numbers) are not associated with any sequence. There is an urgent need to explore the 1525 orphan enzymes (enzymes having EC numbers without an associated sequence) to bridge the wide gap that separates knowledge of biochemical function and sequence information. Strikingly, orphan enzymes can even be found among enzymatic activities successfully used as drug targets. Here, knowledge of sequence would help to develop molecular-targeted therapies, suppressing many drug-related side-effects. Biology is exploring numerous and diverse fields, each of which discovered before, despite intensive research by thousands of is very complex and difficult to study in its entirety. For many people studying the genetics and biochemistry of Saccharomyces years, immense advances in disclosing molecular functions have cerevisiae over the past 50 years. This observation has been con- been made using reductionist approaches, such as molecular firmed repeatedly, with the cohort of genomes that have been biology. Combining genetic, biophysical and biochemical con- sequenced, at a steady pace, over the past ten years. We now know cepts and methodologies has helped to disclose details of com- that many genes have been missed by reductionist approaches plex molecular mechanisms such as DNA replication. -
Annual Report 2014
ANNUAL REPORT 2014 Rajiv Gandhi Centre for Biotechnology Thiruvananthapuram, Kerala Phone: +91 471 2341716, 2347975 Fax: +91 471 2348096, 2346333 E-mail: [email protected] Website: www.rgcb.res.in CONTENTS Director’s Report 05 Cancer Biology Cancer Research Program Laboratory - 1 10 Cancer Research Program Laboratory - 2 22 Cancer Research Program Laboratory - 3 30 Cancer Research Program Laboratory - 4 40 Cancer Research Program Laboratory - 5 51 Cancer Research Program Laboratory - 6 62 Cancer Research Program Laboratory - 7 68 Cancer Research Program Laboratory - 8 71 Cancer Research Program Laboratory - 9 77 Cancer Research Program Laboratory - 10 109 Cardiovascular & Diabetes Disease Biology Programme Cardiovascular Disease Biology Laboratory 117 Diabetes Disease Biology Laboratory 133 Chemical Biology Program Chemical Biology Laboratory - 1 136 Chemical Biology Laboratory - 2 148 Molecular Ecology Laboratory 154 Environmental Biology Laboratory 163 Neurobiology Program Molecular Neurobiology Laboratory 175 Neuro-Stem Cell Biology Laboratory 181 Neuro-Bio-Physics Laboratory 188 Human Molecular Genetics Laboratory 192 Plant Disease Biology & Biotechnology PDBB Laboratory - 1 202 PDBB Laboratory - 2 215 PDBB Laboratory - 3 221 PDBB Laboratory - 4 225 Molecular Reproduction Laboratory - 1 234 Laboratory - 2 250 Tropical Disease Biology Mycobacterium Research Group - 1 259 Mycobacterium Research Group - 2 262 Molecular Virology Laboratory 270 Viral Disease Biology Laboratory -1 276 Viral Disease Biology Laboratory - 2 285 Leptospira -
The Role of the Iterative Modules in Polyketide Synthase Evolution
COMMENTARY COMMENTARY The role of the iterative modules in polyketide synthase evolution Martin Griningera,1 Polyketide synthases (PKSs) assemble activated car- the compound is reached (Fig. 1B). Probably, the best- boxylic acids to elaborate chemical compounds (1). studied representatives are PksA from the fungal genus The key synthetic step is the C-C bond-forming con- Aspergillus, initiating biosynthesis of the environmental densation of an acyl moiety (e.g., acetyl-coenzyme A carcinogen aflatoxin B1 (5), and the 6-methylsalicylic [CoA]) with an α-carboxyacyl moiety (e.g., malonyl- acid synthase (MSAS) from the fungus Penicillium pat- CoA) on release of CO2. The emerging β-ketoacyl ulum (6) (Fig. 1B). compound can optionally be further modified by three Since the synthesis is performed within single multi- accessory catalytic functions. Since this reaction se- domain proteins in recursive manner, the chemical quence can be repeated, with each elongation varying complexity of compounds derived from the iterative in accessory catalytic functions, polyketides can be rich systems is usually less sophisticated compared to in chemistry (Fig. 1A). Many polyketides are of pharma- compounds from the more versatile modular systems. ceutical relevance, among them several top-selling small This is the reason why iterative PKSs usually receive far molecule drugs (2): for example, antibiotics (e.g., eryth- less comment than the modular ones. In their PNAS romycin and tetracycline), antineoplastics (e.g., daunoru- article, Wang et al. (7) extend the relevance of iterative bicin), and immunosuppressants (e.g., rapamycin) (3). PKSs in several aspects: as efficient producers of nat- PKSs are subdivided into three categories: type I ural compounds, as targets for protein engineering, PKSs are large multifunctional proteins composed of and as an inherent part in the evolution of the PKS several catalytic and functional domains, type II PKSs protein family.