Biosynthesis of the Myxobacterial Antibiotic Corallopyronin A

被引:76
作者
Erol, Oezlem [1 ]
Schaeberle, Till F. [1 ]
Schmitz, Alexander [1 ]
Rachid, Shwan [2 ,3 ]
Gurgui, Cristian [4 ]
El Omari, Mustafa [1 ]
Lohr, Friederike [1 ]
Kehraus, Stefan [1 ]
Piel, Joern [4 ]
Mueller, Rolf [2 ,3 ]
Koenig, Gabriele M. [1 ]
机构
[1] Univ Bonn, Inst Pharmaceut Biol, D-53115 Bonn, Germany
[2] Univ Saarland, Dept Pharmaceut Biotechnol, D-66041 Saarbrucken, Germany
[3] Univ Saarland, Helmholtz Inst Pharmaceut Res Saarland, Helmholtz Ctr Infect Res, D-66041 Saarbrucken, Germany
[4] Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany
关键词
antibiotics; biosynthesis; Corallococcus coralloides; corallopyronin A; myxobacteria; polyketides; STRAIN SORANGIUM-CELLULOSUM; ACYL CARRIER PROTEIN; GENE-CLUSTER; FATTY-ACID; PEPTIDE SYNTHETASE; SUBSTRATE-SPECIFICITY; NATURAL-PRODUCT; POLYKETIDE SYNTHASES; ADENYLATION DOMAINS; CONDENSING ENZYME;
D O I
10.1002/cbic.201000085
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Corallopyronin A is a myxobacterial compound with potent antibacterial Feeding experiments with labelled precursors the deduction all biosynthetic building blocks for corallopyronin A and revealed an unusual feature of this metabolite: tits-biosynthesis from two chains, one solely PKS-derived and the other NRPS/PKS-derived. The starter molecule is believed to be carbonic acid or its monomethyl ester, The putative corallopyronin A biosynthetic gene cluster is a trans-AT-type mixed PKS/NRPS gene cluster, containing a beta-branching cassette. Striking features of this gene cluster are a NRPS-like adenylation domain, that, is part of a PKS-type module and is believed to be responsible for glycine incorporation, as well as split modules with individual domains occurring on different genes. It is suggested that CorB is a transacting ketosynthase and it is proposed that it catalyses the Claisen condensation responsible for the interconnection of the two chains. Additionally, the stereochemistry of corallopyronin A was deduced by a combination of a modified Mosher's method and ozonolysis with subsequent chiral GC analyses.
引用
收藏
页码:1253 / 1265
页数:13
相关论文
共 67 条
[1]   Transcription inactivation through local refolding of the RNA polymerase structure [J].
Belogurov, Georgiy A. ;
Vassylyeva, Marina N. ;
Sevostyanova, Anastasiya ;
Appleman, James R. ;
Xiang, Alan X. ;
Lira, Ricardo ;
Webber, Stephen E. ;
Klyuyev, Sergiy ;
Nudler, Evgeny ;
Artsimovitch, Irina ;
Vassylyev, Dmitry G. .
NATURE, 2009, 457 (7227) :332-U8
[2]   Metabolic diversity in myxobacteria:: identification of the myxalamid and the stigmatellin biosynthetic gene cluster of Stigmatella aurantiaca Sg a15 and a combined polyketide-(poly)peptide gene cluster from the epothilone producing strain Sorangium cellulosum So ce90 [J].
Beyer, S ;
Kunze, B ;
Silakowski, B ;
Müller, R .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1999, 1445 (02) :185-195
[3]   Biosynthetic pathway of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinofines [J].
Bredenbruch, F ;
Nimtz, M ;
Wray, V ;
Morr, M ;
Müller, R ;
Häussler, S .
JOURNAL OF BACTERIOLOGY, 2005, 187 (11) :3630-3635
[4]   Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis [J].
Bumpus, Stefanie B. ;
Magarvey, Nathan A. ;
Kelleher, Neil L. ;
Walsh, Christopher T. ;
Calderone, Christopher T. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (35) :11614-+
[5]   Production of the antifungal isochromanone ajudazols A and B in Chondromyces crocatus Cm c5:: Biosynthetic machinery and cytochrome P450 modifications [J].
Buntin, Kathrin ;
Rachid, Shwan ;
Scharfe, Maren ;
Bloecker, Helmut ;
Weissman, Kira J. ;
Mueller, Rolf .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2008, 47 (24) :4595-4599
[6]   Convergence of isoprene and polyketide biosynthetic machinery:: Isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis [J].
Calderone, Christopher T. ;
Kowtoniuk, Walter E. ;
Kelleher, Neil L. ;
Walsh, Christopher T. ;
Dorrestein, Pieter C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (24) :8977-8982
[7]   The biosynthetic genes for disorazoles, potent cytotoxic compounds that disrupt microtubule formation [J].
Carvalho, R ;
Reid, R ;
Viswanathan, N ;
Gramajo, H ;
Julien, B .
GENE, 2005, 359 :91-98
[8]   Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains [J].
Challis, GL ;
Ravel, J ;
Townsend, CA .
CHEMISTRY & BIOLOGY, 2000, 7 (03) :211-224
[9]   Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula [J].
Chang, ZX ;
Sitachitta, N ;
Rossi, JV ;
Roberts, MA ;
Flatt, PM ;
Jia, JY ;
Sherman, DH ;
Gerwick, WH .
JOURNAL OF NATURAL PRODUCTS, 2004, 67 (08) :1356-1367
[10]   Comparative analysis of the complete genome sequence of the plant growth-promoting bacterium Bacillus amyloliquefaciens FZB42 [J].
Chen, Xiao Hua ;
Koumoutsi, Alexandra ;
Scholz, Romy ;
Eisenreich, Andreas ;
Schneider, Kathrin ;
Heinemeyer, Isabelle ;
Morgenstern, Burkhard ;
Voss, Bjoern ;
Hess, Wolfgang R. ;
Reva, Oleg ;
Junge, Helmut ;
Voigt, Birgit ;
Jungblut, Peter R. ;
Vater, Joachim ;
Suessmuth, Roderich ;
Liesegang, Heiko ;
Strittmatter, Axel ;
Gottschalk, Gerhard ;
Borriss, Rainer .
NATURE BIOTECHNOLOGY, 2007, 25 (09) :1007-1014