Novel biologically active natural and unnatural products

Myles, David C.

doi:10.1016/j.copbio.2003.10.013

Cited by 39 publications

(16 citation statements)

References 31 publications

(29 reference statements)

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“…In diesem Zusammenhang haben sich das Auffinden und die Untersuchung von niedermolekularen Naturstoffen als produktiver Ansatz für das Wirkstoff-Design erwiesen. [3] Zwar sind wir offensichtlich noch weit davon entfernt, die evolutionären Kräfte zu verstehen, die die Biosynthesen niedermolekularer Substanzen in Pflanzen, Korallen, Bakterien, Pilzen und höheren Organismen beeinflusst habenzumindest aber können wir feststellen, dass wir mithilfe von Leitsubstanzen aus dem Bereich dieser niedermolekularen Naturstoffe (z. B. Steroide, Prostaglandine, b-Lactame, Polyketide, Aminoglycoside und Statine) die Entwicklung von Wirkstoffen in einem fortgeschritteneren Stadium beginnen können als mithilfe anderer Ansätze wie dem Screening umfangreicher Probensammlungen in Pharmaunternehmen oder von kommerziellen kombinatorischen Bibliotheken.…”

Section: Einführungunclassified

Der Weg zu Fludelon: ein Tumortherapeutikum mit außergewöhnlichen Eigenschaften

Rivkin

Chou

2005

Angewandte Chemie

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Ein Prinzip der Biosynthese von niedermolekularen Naturstoffen ist die Optimierung ihrer Fähigkeit, an bestimmte Proteine oder andere Zielmoleküle zu binden. Die Rahmenbedingungen, innerhalb derer ein zu synthetisierender Wirkstoff funktionieren muss, mögen letztlich ganz anders aussehen – dennoch kann der Einsatz solcher Naturstoffe als Leitsubstanzen zu einem signifikanten Vorsprung bei der Suche nach neuen, klinisch relevanten Wirkstoffen führen. In diesem Kurzaufsatz beschreiben wir, wie die chemische Synthese zu wirksameren Epothilonderivaten führte und wie dies wiederum die Entwicklung neuer Synthesewege inspirierte. Dies demonstriert den Nutzen von zielgerichteten Totalsynthesen bei der Suche nach neuen Wirkstoffen.

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Section: Einführungunclassified

Der Weg zu Fludelon: ein Tumortherapeutikum mit außergewöhnlichen Eigenschaften

Rivkin

Chou

2005

Angewandte Chemie

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“…The bacterial genus Streptomyces is widely known for its ability to produce a variety of secondary metabolites, including valuable antibiotics, anti-tumour agents, immunosuppressants and enzyme inhibitors (Chater 1990;Hopwood, 1987;Strauch et al, 1991;Myles, 2003;Hranueli et al, 2005). A secondary metabolite produced by Streptomyces sp.…”

Section: Introductionmentioning

confidence: 99%

Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. CK4412

et al. 2007

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The bacterial genus Streptomyces has long been appreciated for its ability to produce various kinds of medically important secondary metabolites, such as antibiotics, anti-tumour agents, immunosuppressants and enzyme inhibitors. Tautomycetin (TMC), which is produced by Streptomyces sp. CK4412, is a novel activated T cell-specific immunosuppressive compound with an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. Using a Streptomyces polyketide methylmalonyl-CoA acyltransferase gene as a probe, three overlapping cosmids were isolated from the genomic library of TMC-producing Streptomyces sp. CK4412. Sequence information of an approximately 70 kb contiguous DNA region revealed two multi-modular type I polyketide synthases (PKSs), and 12 additional gene products presumably involved in TMC biosynthesis. The deduced roles for most of the TMC PKS catalytic domains were consistent with the expected functions necessary for TMC chain elongation and processing. In addition, disruption of a putative TMC acyl-CoA transferase gene, located upstream of the PKS gene locus, completely abolished TMC biosynthesis. Taken together, these data provide strong supporting evidence that the cloned gene cluster identified in this study is responsible for TMC biosynthesis in Streptomyces sp. CK4412, and set the stage for detailed genetic and biochemical studies of the biosynthesis of this important metabolite.

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“…They are widely used as natural sources of a variety of commercially valuable enzymes and secondary metabolites, including antibiotics, antitumor agents, immunosuppressants, and enzyme inhibitors (3,6,8,15,16). The regulation of secondary metabolite production in Streptomyces species involves multiple and parallel regulatory networks that are complicatedly intertwined and sensitive to both nutritional and environmental factors (2,4,19).…”

mentioning

confidence: 99%

Putative TetR Family Transcriptional Regulator SCO1712 Encodes an Antibiotic Downregulator in Streptomyces coelicolor

Lee

Huang

et al. 2010

Appl Environ Microbiol

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A tetR family transcriptional regulatory gene (SCO1712) was identified as a global antibiotic regulatory gene from a Streptomyces interspecies DNA microarray analysis. SCO1712 disruption in S treptomyces coelicolor not only upregulated antibiotic biosynthesis through pathway-specific regulators when a previously identified pleiotropic downregulatory wblA was expressed but also further stimulated antibiotic production in a wblA deletion mutant, implying that SCO1712 might encode a novel antibiotic downregulator.

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Novel biologically active natural and unnatural products

Cited by 39 publications

References 31 publications

Der Weg zu Fludelon: ein Tumortherapeutikum mit außergewöhnlichen Eigenschaften

Der Weg zu Fludelon: ein Tumortherapeutikum mit außergewöhnlichen Eigenschaften

Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. CK4412

Putative TetR Family Transcriptional Regulator SCO1712 Encodes an Antibiotic Downregulator in Streptomyces coelicolor

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