NPR View Article Online REVIEW View Journal | View Issue Natural products containing ‘decalin’ motif in microorganisms Cite this: Nat. Prod. Rep.,2014,31,1175 Gang Li,† Souvik Kusari†* and Michael Spiteller* Covering: up to February 2014 Microorganisms are well-known producers of a wide variety of bioactive compounds that are utilized not only for their primary metabolism but also for other purposes such as defense, detoxification, or communication with other micro- and macro-organisms. Natural products containing a ‘decalin ring’ occur often in microorganisms. They exhibit diverse and remarkable biological activities, including antifungal, antibacterial, anticancer and immunosuppressive activities, to name a few. This review surveys Received 19th March 2014 the natural decalin-type compounds that have been isolated from microorganisms, with emphasis on DOI: 10.1039/c4np00031e Creative Commons Attribution-NonCommercial 3.0 Unported Licence. both chemical and biological implications. Total syntheses of some important decalin moiety-containing www.rsc.org/npr natural products are also highlighted. 1 Introduction 1 Introduction 2 Structural classication 3 Polyketide decalin The ‘decalin’ motif is found in an array of secondary metabo- 3.1 Monacolins lites produced by microorganisms, mainly fungi and actino- 3.2 Monacolin derivatives mycetes. It is usually correlated with highly multi- This article is licensed under a 3.3 Side chains with a 3-oxopropanol or its derivative functionalized or architecturally complex groups, thereby 3.4 Side chains with a pentanedienoic acid demonstrating surprising structural and functional diversity. 3.5 Decalins with oxygenated diene/triene/tetraene side Their intricate structures and diverse biological activities have chains attracted researchers around the world to investigate their Open Access Article. Published on 02 July 2014. Downloaded 9/29/2021 8:24:40 PM. 3.6 Pyrone derivatives biosynthesis, chemical synthesis, and the various facets of the 3.7 Macrolides functionalized decalin skeleton.1–3 3.8 Pyrrolidine-2-one The decalin scaffold is primarily biosynthesized by microor- 3.9 4-Hydroxy-2-pyridone alkaloids ganisms based on two biosynthetic derivations, isoprenoids 3.10 Spirotetronates (mevalonate) and polyketides (acetate). Isoprenoid-derived dec- 3.11 Pyrrolizidines alins typically belong to natural sesquiterpenoids and diterpe- 3.12 Others noids, and have been thoroughly covered in a series of reports by 4 Isoprenoid decalin Fraga4 and Hanson.5,6 However, there is a dearth of comprehen- 5 Conclusions sive reviews on polyketide decalin-derived secondary metabolites, 6 Acknowledgements either about their isolation and biological activities, or related 7 References syntheses. Furthermore, no critical observation about the differences or similarities of these decalin moiety-containing compounds from a microbial origin has been reported. The polyketide decalin skeleton in some fungal or bacterial secondary metabolites is proposed to be biosynthesized by an enzymatic intramolecular Diels–Alder (IMDA) cycloaddition.1,7 However, only ve potential or possible Diels–Alderase enzymes 7,8 Institute of Environmental Research (INFU), Department of Chemistry and Chemical have been puried until now, of which lovastatin nonaketide Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund, synthase (LovB) and solanapyrone synthase (SPS) are proposed Otto-Hahn-Str.6, 44221 Dortmund, Germany. E-mail: souvik.kusari@infu. to be related to the decalin formation of lovastatin and sol- tu-dortmund.de; [email protected]; Fax: +49-231-755-4084; +49-231- anapyrone A.9,10 It should be noted that the non-enzymatic 755-4085; Tel: +49-231-755-4086; +49-231-755-4080 † These authors contributed equally to this work. catalytic synthesis of decalin in biological systems is also This journal is © The Royal Society of Chemistry 2014 Nat. Prod. Rep.,2014,31, 1175–1201 | 1175 View Article Online NPR Review possible, as suggested in a biomimetic total synthesis of the double bonds. Many other moieties such as small lactone ring, decalin compound (Æ)-UCS1025A.11 Based on the IMDA reac- pyrone, tetramic acid, unusual sugars, pyridone, tetronic acid, tion of a substrate,9 all possible cyclization types to decalin are or pyrrolizidine act as diverse moieties, and are usually found in shown in Scheme 1. There are four comprehensive reviews on this type of compound. With the occurrence and interaction of the syntheses of trans-orcis-decalins mainly in isoprenoids these functional units in structures, a complex macrocycle or (mevalonate)-derived natural products.3,12–14 However, to the polycycle that is oen fused with the decalin ring, is formed in best of our knowledge, reviews compiling different facets of the microbial secondary metabolites. In this manuscript, those polyketide decalin have not been reported. secondary metabolites are mainly classied according to the Therefore, given the present gaps in a comprehensive elab- proposed biosynthesis of the decalin moiety-containing oration of the ‘decalin’ system and considering their intriguing compounds: polyketide or isoprenoid biosynthetic derivations. structural and biological features, the target of this review is to The compounds with polyketide or isoprenoid decalin motifs provide an informative overview of the topic that can serve as a are further classied according to the features of the remaining point of reference for an understanding of the functions and side chain or diverse moieties. applications of decalin. 2 Structural classification 3 Polyketide decalin Fungi and bacteria are the major microbial resources that Decalin, as a ring system or scaffold, can be greatly modied by produce the decalin moiety-containing secondary metabolites many functional groups, such as a side chain, or diverse with a broad spectrum of biological activities. Most of these moieties. The side chains are usually substituted by many compounds have a polyketidic decalin scaffold. Frequently, they functional groups such as hydroxyl, carboxyl, or C]C and C]O are highly functionalized through the substitution of methyl, hydroxyl, or C]C and C]O double bonds on the decalin Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Gang Li received his B.Sc. degree skeleton, or through a three-, ve-, or seven-membered side (2009) at Shandong University of chain with carboxyls (or its ester), several double bonds, or via Traditional Chinese Medicine ring formation. Furthermore, a pyrone moiety connected to a and M.Sc. degree (2012) under poly-substituted decalin nucleus by a carbon–carbon bond the supervision of Prof. Hong- contributes to an important class of polyketide natural prod- Xiang Lou from Shandong ucts. In addition, the pyrrolidine-2-one moieties such as tetra- University, China. He is presently mic acids and the 4-hydroxy-2-pyridone group are important working at INFU, TU Dortmund, functionalized units found in many polyketide decalin natural This article is licensed under a Germany for his doctorate with a products. The promising biosynthetic potential of fungi is also fellowship from the China Schol- elaborated here with several examples of macrocyclic or poly- arship Council (CSC). His cyclic compounds. research focuses on bioactive The biosynthesis of secondary metabolites with a polyketide Open Access Article. Published on 02 July 2014. Downloaded 9/29/2021 8:24:40 PM. secondary metabolites from decalin system is attributed to single or mixed biosynthetic endophytic fungi. pathways. Specically, these compounds are proposed to be Souvik Kusari received bachelor Michael Spiteller received his and master degrees in Biotech- Diploma in Chemistry (1976) nology from Bangalore Univer- from the Georg-August-Uni- sity, India. He then earned a versitat¨ in Gottingen,¨ Germany doctorate in Natural Sciences where he earned a doctorate in from INFU, TU Dortmund, Ger- Chemistry in 1979. Aer Habil- many in 2010. Aer working as a itation in Soil Science, he joined scientist in the same institute for the Institute for Metabolism and over two years, he became a Environmental Fate, Bayer visiting researcher at the Corp., Germany for 8 years as a Department of Plant Sciences, Group Leader. He then joined University of Oxford, UK for a the University of Kassel as a full year in 2013. He is also a Professor and is now Professor visiting lecturer at the University of Yaound´e 1, Cameroon, Africa and Head of INFU, TU Dortmund, Germany. He is involved in since 2012 within the scope of the DAAD “Welcome to Africa” various projects dealing with natural product drug discovery from initiative. His research interests include characterization of fungal plants and endophytes, structural identication of unknown and bacterial endophytes to evaluate their diversity, chemical xenobiotics and their metabolites, metabolism of pesticides in the ecology and biosynthetic pathways. environment, and veterinary drugs. 1176 | Nat. Prod. Rep.,2014,31,1175–1201 This journal is © The Royal Society of Chemistry 2014 View Article Online Review NPR Scheme 1 The IMDA reaction to decalin. assembled by a linear polyketide unit, which are then cyclized compound as mevinolin isolated from A. terreus19). The lova- by an enzymatic or non-enzymatic IMDA cycloaddition to form statin biosynthetic gene cluster was rst identied in 1999 by the decalin scaffold.1,7 Prior to or aer cyclization, many func- the groups of Vederas and Hutchinson. Aer this work, more Creative Commons Attribution-NonCommercial 3.0