These three criteria of secondary metabolites are true only in the ideal case. The confusion between the ideal case and the reality is one of the reasons for our uneasiness about the term secondary metabolism. Perhaps it would be bet ter and less confusing to speak of a general and a special metabolism, rather than of a pr imary and a secondary metabolism. The second reason for uneasiness is our view of evolution. In our view of evolution there is no place for things without a function. Things without a function cannot exist over a long period of time, nor in large variability, nor often in large amounts; they must be eliminated. A reconciliation of these divergent ideas of our views of evolution and the observable reality of the secondary metabolism is the aim of this lecture. In focusing on general aspects of biology, molecular biology has a tendency to forget or to overlook aspects of a given specific part of biology. I t would be an exaggeration to suggest tha t only what is important for Escherichia coli can also be important for the elephant. The renaissance of organismic biology should or bet ter could also be a renaissance of secondary metabolism. The biological l i terature offers differing hypotheses for the role of the secondary metabolism. I will briefly evaluate each of these hypotheses.

What are secondary metabolites

Lichens are a world-widespread consortium of fungal and photosynthetic partners. Usnic acid is one of the most common and abundant lichen metabolites, well known as an antibiotic, but also endowed with several other interesting properties. This review summarises the most relevant studies on usnic acid, focusing on a number of biological activities in different fields. On the basis of the existing literature, usnic acid seems to be an exclusive lichen product. No synthetic derivatives more effective than the natural form are known. Both the (+) and (–) enantiomers of usnic acid are effective against a large variety of Gram-positive (G+) bacterial strains, including strains from clinical isolates, irrespective of their resistant phenotype. Of particular relevance is the inhibition of growth of multi-resistant strains of Streptococcus aureus, enterococci and mycobacteria. The (+)-usnic acid enantiomer appears to be selective against Streptococcus mutans without inducing perturbing side effects on the oral saprophyte flora. On the other hand, the (–)-usnic acid enantiomer is a selective natural herbicide because of its blocking action against a specific key plant enzyme. Other recognised characteristics of usnic acid are ultraviolet absorption and preserving properties. The toxicology, the in vitro anti-inflammatory effects and the mechanism of action of usnic acid need to be investigated in greater detail in order to reach clinical trials and to allow further applications. Furthermore, more research is needed to make possible intensive lichen culture, in order to produce large quantities of lichen substances for pharmaceutical, cosmetic and agricultural purposes. Some biological aspects, i.e. the possible biological roles of usnic acid, are discussed.

A review on usnic acid, an interesting natural compound.

N-Hydroxylation: A new metabolic reaction observed in the rat with the carcinogen 2-acetylaminofluorene.

Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Xanthones from Fungi, Lichens, and Bacteria: The Natural Products and Their Synthesis

Lichen-forming fungi are unique organisms, producing biologically active metabolites with a great variety of effects, including antibiotic, antimycobacterial, antiviral, anti-inflammatory, analgesic, antipyretic, antiproliferative and cytotoxic activities. However, only very limited numbers of lichen substances have been screened for their biological activities and their therapeutic potential in medicine. This is certainly due to the difficulties encountered in identification of the species, collection of bulk quantities, and the isolation of pure substances for structure determination and testing activity. Recently, possibilities for bypassing some of these former difficulties have arisen by the introduction of new techniques. This includes axenic cultivation for production of the genuine compounds or new ones, extraction of focused compounds, or synthesis of natural products or their derivatives for testing. Utilizing these new opportunities, the discovery of novel active metabolites, which could serve as lead compounds, is significantly facilitated. At the same time, the evolution of secondary metabolite patterns is studied using phylogenetic approaches. Yet, the genetic background of the complex chemical patterns is poorly understood. The scattered occurrence of some compounds suggests that their production evolved either in parallel or that ancient biosynthetic pathways are abandoned in many lineages. At least, studies on polyketide synthase genes from different lichen groups suggest a high level of gene paralogy. In this context, clades of orthologous polyketide synthase genes, which are often shared with distantly related non-lichenized fungi, can roughly be identified by their sequence similarity and their similar patterns of substitution rates. The functional assignment of paralogs is nevertheless difficult and reasonable only in a few cases. A global approach of the lichen metabolomic features appears to be essential in developing new and viable biotechnological processes which could afford suitable amounts of unique lichen compounds.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S1479262105000328

Lichens—a promising source of bioactive secondary metabolites

Aus den Wurzeln der nordamerikanischen Komposite Echinacea angustifolia D. C. konnte eine wasserlosliche, kristallisierte Verbindung C35H46O20 in einer Ausbeute von ca. 1% isoliert werden. Dieses mit Echinacosid bezeichnete Naturprodukt ist optisch aktiv ([α] = −56,5°, in Wasser) und besitzt eine schwache antibakterielle Wirksamkeit gegenuber Staphylococcus aureus und Streptokokken.

Isolierung und Konstitution des Echinacosids, eines Glykosids aus den Wurzeln von Echinacea angustifolia D. C. 6. Mitteilung über antibakterielle Stoffe

Durch Kultur des Penicilliumstammes 889 auf einer Nahrlosung, die als Kohlenstoffquelle ausschliesslich Rhamnose enthielt, wurde ein Enzym gebildet, das Proscillaridin A in das bisher unzugangliche primare Aglykon Scillarenin und Rhamnose spaltet. Durch Oxydation der im Scillarenin erhaltenen Hydroxylgruppe an C3 konnte ein α,β-ungesattigtes Keton gewonnen werden, das sich als identisch erwies mit dem Anhydro-telocinobufagon, einem Abbauprodukt des Krotengiftes Telocinobufagin. Da in beiden Praparaten der doppelt ungesattigte sechsgliedrige Lactonring unversehrt geblieben ist, so beweist ihre Identitat, dass Scillaglykoside und Krotengifte dieselbe Lactonseitenkette besitzen.

Darstellung von Scillarenin, dem primären Aglykon von Scillaren A, mit Hilfe eines adaptiven Enzyms. 28. Mitteilung über Herzglykoside

Aus dem Gemisch der gelben Farbstoffe des Mutterkorns konnte die Secalonsaure und eine dieser nahestehenden Verbindung, die wir Chrysergonsaure nennen, in kristallisiertem Zustand isoliert werden. Es werden die Eigenschaften der beiden Naturstoffe sowie Abbaureaktionen beschrieben. Die Secalonsaure besitzt wahrscheinlich die Bruttoformel C31H30–32O14, die Chrysergonsaure C32H30–32O14. Beide Verbindungen sind optisch aktiv. Beim Erhitzen mit Essigsaureanhydrid entsteht aus Secalonsaure ein farbloses Spaltprodukt der Zusammensetzung C17H14–16O7, aus Chrysergonsaure ein entsprechendes Spaltstuck C15H14–16O7. Bei der Alkalischmelze konnten aus den beiden gelben Farbstoffen Bernsteinsaure, Brenzweinsaure und 2,4,2′,4′-Tetraoxy-diphenyl erhalten werden.

Über gelbe Farbstoffe im Mutterkorn. 11. Mitteilung über antibakterielle Stoffe

Die Glykoside Scillaren A und Proscillaridin A sind durch einen Penicilliumstamm in einer Nahrlosung, die als einzige Kohlenstoffquelle Rhamnose enthielt, nicht nur bis zum Scillarenin, sondern uberwiegend bis zum entsprechenden Keton, dem Scillarenon, abgebaut worden. Wird die Ketogruppe des Scillarenons, dessen Kerndoppelbindung zwischen den C-Atomen 4 und 5 liegt, nach Meerwein-Ponndorf reduziert, so entsteht Scillarenin, was beweist, dass sich auch die Kerndoppelbindung im Scillarenin zwischen den C-Atomen 4 und 5 befinden muss. Das primare Aglykon Scillarenin, bzw. die sich davon ableitenden Glykoside Proscillaridin A, Scillaren A und Glucoscillaren A besitzen die Konstitution, wie sie im Formelbild I wiedergegeben ist.

Die Lage der Kerndoppelbindung im Scillarenin. 32. Mitteilung über Herzglykoside

Enzympraparate aus zahlreichen Stammen niederer Pilze aus der Gruppe der Hyphomycetales sowie von Claviceps purpurea (Ascomycetes) vermogen aus glucosehaltigen Herzglykosiden die Glucose abzuspalten. Das Scillirosid, das als Zuckerkomponente nur Glucose enthalt, wird bis zum Aglykon, Scillirosidin abgebaut. Stamme der Gattungen Penicillium und Aspergillus erwiesen sich als besonders reich an herzglykosidspaltenden Enzymen.

A. Brack

Papers

Isolierung und Konstitution des Echinacosids, eines Glykosids aus den Wurzeln von Echinacea angustifolia D. C. 6. Mitteilung über antibakterielle Stoffe

Darstellung von Scillarenin, dem primären Aglykon von Scillaren A, mit Hilfe eines adaptiven Enzyms. 28. Mitteilung über Herzglykoside

Über gelbe Farbstoffe im Mutterkorn. 11. Mitteilung über antibakterielle Stoffe

Die Lage der Kerndoppelbindung im Scillarenin. 32. Mitteilung über Herzglykoside

Spaltung von Herzglykosiden durch Pilzenzyme. 24. Mitteilung über Herzglykoside