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Biosynthesis and Function of Secondary Metabolites Biosynthesis and function of secondary metabolites Edited by Jeroen S. Dickschat Generated on 11 October 2021, 10:46 Imprint Beilstein Journal of Organic Chemistry www.bjoc.org ISSN 1860-5397 Email: [email protected] The Beilstein Journal of Organic Chemistry is published by the Beilstein-Institut zur Förderung der Chemischen Wissenschaften. This thematic issue, published in the Beilstein Beilstein-Institut zur Förderung der Journal of Organic Chemistry, is copyright the Chemischen Wissenschaften Beilstein-Institut zur Förderung der Chemischen Trakehner Straße 7–9 Wissenschaften. The copyright of the individual 60487 Frankfurt am Main articles in this document is the property of their Germany respective authors, subject to a Creative www.beilstein-institut.de Commons Attribution (CC-BY) license. Biosynthesis and function of secondary metabolites Jeroen S. Dickschat Editorial Open Access Address: Beilstein J. Org. Chem. 2011, 7, 1620–1621. Institut für Organische Chemie, Technische Universität doi:10.3762/bjoc.7.190 Carolo-Wilhelmina zu Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany Received: 20 October 2011 Accepted: 25 October 2011 Email: Published: 05 December 2011 Jeroen S. Dickschat - [email protected] This article is part of the Thematic Series "Biosynthesis and function of secondary metabolites". Guest Editor: J. S. Dickschat © 2011 Dickschat; licensee Beilstein-Institut. License and terms: see end of document. Natural products have long been used by humans owing to their situation started to change at the beginning of the 19th century, beneficial effects. Indulgences such as coffee and tea, with their when Friedrich Wilhelm Adam Sertürner (1783–1841) first moderate stimulatory properties, have a long cultural tradition isolated morphine from opium, naming it after Morpheus, the and are today some of the most important agricultural products Greek god of dreams and demonstrating its activity in self-tests, worldwide. Other drugs have much stronger impacts on the as was typical practice during these early times of chemistry. A central nervous system. For example, coca was originally used likewise important discovery was made by Alexander Fleming by the Inca civilisation because of its strong stimulatory effects, (1881–1955), who isolated the antibiotic penicillin from the which result in feelings of happiness and euphoria. Opium was mould Penicillium notatum in a groundbreaking contribution, used by many ancient cultures as an efficient analgesic, but this which was awarded the Nobel Prize in 1945. also illustrates one of the first examples of drug abuse as it was used by warriors as an anxiolytic when girding their loins. The discovery of new bioactive natural products is still a fascin- Besides their pleasant traits these highly active drugs have ating field in organic chemistry as demonstrated by the recent adverse side effects, including most importantly an extremely paradigms of the anticancer drug epothilon, the immunosup- high potential to cause addiction in combination with physical pressant rapamycin, or the proteasome inhibitor salinospor- and mental prostration upon long-term abuse. Therefore, the amide, to name but a few of hundreds of possible examples. production, importation, trading, and possession of these drugs Finding new secondary metabolites is a prerequisite for the are today under strict control by public authorities. Another development of novel pharmaceuticals, and this is an especially historically interesting example of drug misuse is given by the urgent task in the case of antibiotics due to the rapid spreading death penalty imposed on Socrates in 399 B.C., carried out by of bacterial resistances and the emergence of multiresistant the forced ingestion of the proverbial cup of hemlock. pathogenic strains, which poses severe clinical problems in the treatment of infectious diseases. This Thematic Series on the These traditional and historical examples of the usage of biosynthesis and function of secondary metabolites deals with bioactive natural products all originated in the ancient cultures, the discovery of new biologically active compounds from all without any knowledge about the underlying chemistry. This kinds of sources, including plants, bacteria, and fungi, and also 1620 Beilstein J. Org. Chem. 2011, 7, 1620–1621. with their biogenesis. Biosynthetic aspects are closely related to functional investigations, because a deep understanding of License and Terms metabolic pathways to natural products, not only on a chemical, This is an Open Access article under the terms of the but also on a genetic and enzymatic level, allows for the expres- Creative Commons Attribution License sion of whole biosynthetic gene clusters in heterologous hosts. (http://creativecommons.org/licenses/by/2.0), which This technique can make interesting, new secondary metabol- permits unrestricted use, distribution, and reproduction in ites available from unculturable microorganisms, or may be any medium, provided the original work is properly cited. used to optimise their availability by fermentation, for further research and also for production in the pharmaceutical industry. The license is subject to the Beilstein Journal of Organic Especially fascinating is the intrinsic logic of the polyketide and Chemistry terms and conditions: nonribosomal peptide biosynthetic machineries, which is (http://www.beilstein-journals.org/bjoc) strongly correlated with the logic of fatty acid biosynthesis as part of the primary metabolism. Insights into the mechanisms of The definitive version of this article is the electronic one modular polyketide and nonribosomal peptide assembly lines which can be found at: open up the possibility for direct modifications, e.g., of oxi- doi:10.3762/bjoc.7.190 dation states of the natural product’s carbon backbone by simple domain knockouts within the responsible megasyn- thases, or the introduction of a variety of alternative biosyn- thetic starters by mutasynthesis approaches, thus leading to new variants of known metabolites, which may have improved prop- erties for therapeutic use. Another interesting aspect is the usage of enzymes in chemical transformations, which can provide synthetic organic chemists with an efficient access route to typically chiral building blocks that may otherwise be difficult to obtain. It is my great pleasure to thank all of the contributors to this Thematic Series, the staff of the Beilstein-Institut, and my esteemed colleague and teacher Prof. Henning Hopf (Braunschweig) for opening the opportunity to guest-edit the present issue. Enjoy reading it! Jeroen S. Dickschat Braunschweig, October 2011 1621 Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes Jan-Christoph Kehr, Douglas Gatte Picchi and Elke Dittmann* Review Open Access Address: Beilstein J. Org. Chem. 2011, 7, 1622–1635. University of Potsdam, Institute for Biochemistry and Biology, doi:10.3762/bjoc.7.191 Karl-Liebknecht-Str. 24/25, 14476 Potsdam-Golm, Germany Received: 22 July 2011 Email: Accepted: 19 September 2011 Jan-Christoph Kehr - [email protected]; Douglas Gatte Picchi - Published: 05 December 2011 [email protected]; Elke Dittmann* - [email protected] This article is part of the Thematic Series "Biosynthesis and function of * Corresponding author secondary metabolites". Keywords: Guest Editor: J. S. Dickschat cyanobacteria; natural products; NRPS; PKS; ribosomal peptides © 2011 Kehr et al; licensee Beilstein-Institut. License and terms: see end of document. Abstract Cyanobacteria are prolific producers of natural products. Investigations into the biochemistry responsible for the formation of these compounds have revealed fascinating mechanisms that are not, or only rarely, found in other microorganisms. In this article, we survey the biosynthetic pathways of cyanobacteria isolated from freshwater, marine and terrestrial habitats. We especially empha- size modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights obtained from the biochemical studies of cyanobacterial pathways can inspire the development of concepts for the design of bioactive compounds by synthetic-biology approaches in the future. Introduction The role of cyanobacteria in natural product research Cyanobacteria flourish in diverse ecosystems and play an enor- [2] (Figure 1). Other cyanobacteria show a strong tendency for mous role in the biogeochemical cycles on earth. They are mass developments during summer months, so-called blooms found in marine, freshwater and terrestrial environments and [3] (Figure 1). Cyanobacteria do not belong to the established even populate such extreme habitats as the Antarctic or hot sources of natural products and are only incidentally screened springs [1]. Due to their capability to fix nitrogen from the by pharmaceutical industries. For a long time, natural product atmosphere some species are attractive partners in symbioses research on cyanobacteria was mostly focused on toxins, in par- 1622 Beilstein J. Org. Chem. 2011, 7, 1622–1635. Figure 1: Cyanobacteria proliferate in diverse habitats. A) Bloom-forming freshwater cyanobacteria of the genus Microcystis. B) Roots of cyanobacte- rial symbiosis host Cycas circinalis. C) Terrestrial cyanobacteria living in corraloid
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