Review Convergence in the biosynthesis of acetogenic natural products from plants, fungi, and bacteria Gerhard Bringmann a, * , Andreas Irmer a , Doris Feineis a , Tobias A.M. Gulder a , Hans-Peter Fiedler b a Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany b Institute of Microbiology, University of Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany article info Article history: Received 31 March 2009 Received in revised form 5 August 2009 Available online 26 September 2009 Dedicated to Wolfdieter Schenk on the occasion of his 65th birthday Keywords: Triphyophyllum peltatum Kniphofia sp. Drechslera catenaria Galeruca tanazeti Nocardia Streptomyces Biosynthesis Feeding experiments Anthraquinones Naphthylisoquinoline alkaloids Polyketides Chrysophanol Harris–Franck ketone (genoketide A1) Dioncophylline A abstract This review deals with polyketides to which nature has developed different biosynthetic pathways in the course of evolution. The anthraquinone chrysophanol is the first example of an acetogenic natural prod- uct that is, in an organism-specific manner, formed via more than one polyketide folding mode: In eukaryotes, like e.g., in fungi, in higher plants, and in insects, it is synthesized via folding mode F, while in prokaryotes it originates through mode S. It has, more recently, even been found to be synthesized by a third pathway, named mode S 0 . Thus, chrysophanol is the first polyketide synthase product that origi- nates through a divergent–convergent biosynthesis (depending on the respective producing organisms). A second example of a striking biosynthetic convergence is the isoquinoline alkaloids. While all as yet investigated representatives of this large family of plant-derived metabolites (more than 2500 known representatives!) are formed from aromatic amino acids, the biosynthetic origin of naphthylisoquinoline alkaloids like dioncophylline A is unprecedented in following a route to isoquinolines in plants: we have shown that such naphthylisoquinolines represent the as yet only known polyketidic di- and tetrahydro- isoquinolines, originating from acetate and malonate units, exclusively. Both molecular halves, the iso- quinoline part and the naphthalene portion, are even synthesized from a joint polyketide precursor, the first proven case of the F-type folding mode in higher plants. The biosynthetic origins of the natural products presented in this paper were elucidated by feeding 13 C 2 -labeled acetate (or advanced precur- sors) to the respective producing organisms, with subsequent NMR analysis of their 13 C 2 incorporation patterns using the potent cryoprobe methodology, thus making the full polyketide folding pattern visible. Ó 2009 Elsevier Ltd. All rights reserved. Contents 1. Introduction ........................................................................................................ 1776 2. Biosynthesis of the anthraquinone chrysophanol and the phenylanthraquinone knipholone........................................ 1778 3. Biosynthesis of naphthylisoquinoline alkaloids ............................................................................ 1781 4. Convergence in natural products biosynthesis – conclusion and outlook ....................................................... 1783 Acknowledgements .................................................................................................. 1784 References ......................................................................................................... 1784 1. Introduction Fused-ring aromatic polyketides constitute a large group of sec- ondary metabolites with remarkable structural diversity and phar- macological properties, biosynthetically arising from small acyl units that get assembled by polyketide synthases (PKSs) (Rawlings, 1999; Staunton and Weissman, 2001; Thomas, 2004; Hertweck et al., 2007). In the past, polyketidic natural products have pro- vided many promising leads for clinical and industrial develop- ment of important and widely used pharmaceutical agents or agrochemicals, and they still do represent a major source for struc- turally novel bioactive target molecules (Dewick, 2002; O’Hagan, 1991). They are widely distributed not only in fungi, lichens, and 0031-9422/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2009.08.019 * Corresponding author. Tel.: +49 931 888 5323; fax: +49 931 888 4755. E-mail address: bringman@chemie.uni-wuerzburg.de (G. Bringmann). Phytochemistry 70 (2009) 1776–1786 Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem