Biosynthesis and function of secondary metabolites
The discovery of new bioactive natural products is still a fascinating field in organic chemistry as demonstrated by the recent paradigms of the anticancer drug epothilon, the immunosuppressant rapamycin, or the proteasome inhibitor salinosporamide, to name but a few of hundreds of possible examples. Finding new secondary metabolites is a prerequisite for the development of novel pharmaceuticals, and this is an especially urgent task in the case of antibiotics due to the rapid spreading of bacterial resistances and the emergence of multiresistant pathogenic strains, which poses severe clinical problems in the treatment of infectious diseases. This Thematic Series on the biosynthesis and function of secondary metabolites deals with the discovery of new biologically active compounds from all kinds of sources, including plants, bacteria, and fungi, and also with their biogenesis. Biosynthetic aspects are closely related to functional investigations, because a deep understanding of metabolic pathways to natural products, not only on a chemical, but also on a genetic and enzymatic level, allows for the expression of whole biosynthetic gene clusters in heterologous hosts. This technique can make interesting, new secondary metabolites available from unculturable microorganisms, or may be used to optimise their availability by fermentation, for further research and also for production in the pharmaceutical industry.
See also the Thematic Series:
Natural products in synthesis and biosynthesis II
Natural products in synthesis and biosynthesis
- Review
- Published 05 Dec 2011
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Figure 1: Cyanobacteria proliferate in diverse habitats. A) Bloom-forming freshwater cyanobacteria of the gen...
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Figure 2: Schematic representation of enzymatic domains in A) nonribosomal peptide synthetases (NRPS); B) pol...
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Figure 3: Structures of NRPS and PKS products in freshwater cyanobacteria.
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Figure 4: A) Synthesis of the Adda ((2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic...
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Figure 5: Structures of NRPS and PKS products in marine cyanobacteria.
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Figure 6: A) Formation of the trichloroleucyl starter unit of barbamide (7) synthesis through the non-heme ir...
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Figure 7: Structures of NRPS and PKS products in terrestrial cyanobacteria.
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Figure 8: Synthesis of the (2S,4S)-4-methylproline moiety of nostopeptolides A (13).
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Figure 9: Structures of cyanobacterial peptides that are synthesized ribosomally and post-translationally mod...
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Figure 10: Formation of ester linkages and ω-amide linkage in microviridins 17 by the ATP grasp ligases MvdD a...
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Figure 11: Structures of cyanobacterial sunscreen compounds.
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- Letter
- Published 05 Dec 2011
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Scheme 1: Secondary metabolites 1–4 isolated from Stachylidium sp.
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- Letter
- Published 05 Dec 2011
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Scheme 1: Catalytic cycle of α-KG dependent oxygenases.
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Scheme 2: Selectivities and relative yields in conversions of (a) L-proline (defined as 100% yield) and (b) t...
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Figure 1: Typical HPLC-chromatograms of the conversions of (a) trans-3-methyl-L-proline and (b) L-proline und...
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- Full Research Paper
- Published 20 Dec 2011
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Scheme 1: Fatty acid biosynthesis.
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Figure 1: Volatile methyl esters from bacteria.
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Figure 2: Compounds found in the headspace extracts of M. aurantiaca.
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Figure 3: Total ion chromatograms of the headspace extract from M. aurantiaca (A), and expansions of the tota...
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Figure 4: FAMEs identified in the headspace extracts from M. aurantiaca.
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Figure 5: Mass spectra of (A) methyl dodecanoate (83), (B) methyl 2-methyldodecanoate (10), (C) methyl 4-meth...
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Scheme 2: McLafferty fragmentation of FAMEs.
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Figure 6: The functional group increment FG(n)FAME, HP-5 MS.
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Scheme 3: Synthesis of FAMEs identified from M. aurantiaca.
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Scheme 4: Synthesis of the γ- and (ω−3)-methyl branched FAME 114.
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Figure 7: Mass spectra of tentatively identified methyl 4,8-dimethyldodecanoate (115) and methyl 8-ethyl-4-me...
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- Full Research Paper
- Published 21 Feb 2012
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Figure 1: UPLC–ESIMS-based metabolic profiles of Gracilaria vermiculophylla (A) and Gracilaria chilensis (B) ...
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Scheme 1: 5-((1E,3,5E,7Z,10Z)-hexadeca-1,3,5,7,10-pentaenyl)dihydrofuran-2(3H)-one (5) with 1H–1H COSY (bold ...
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Scheme 2: Suggested pathway for the biosynthesis of 5.
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Figure 2: Relative risk (mean ± 95% confidence interval) of Echinolittorina peruviana attachment on surfaces ...
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- Full Research Paper
- Published 22 Feb 2012
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Figure 1: Volatile compounds released by Mycobacterium tuberculosis and M. bovis identified in previous studi...
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Figure 2: Total ion chromatogram of a headspace extract of a culture of Mycobacterium tuberculosis strain 2, ...
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Figure 3: Volatiles released by mycobacteria and Nocardia spp. grown on a 7H11 solid medium.
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Figure 4: Volatiles released by M. tuberculosis grown in a 7H9 broth liquid medium.
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- Full Research Paper
- Published 04 Apr 2012
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Figure 1: The endophenazine biosynthetic gene cluster from Streptomyces anulatus 9663 and the structures of p...
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Figure 2: Production of prenylated phenazines after heterologous expression of the endophenazine gene cluster...
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Figure 3: HPLC analysis of mycelia of the heterologous expression strain S. coelicolor M512(ppzOS04) after fi...
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Figure 4: Extracted ion chromatograms for the mass of endophenazine B (m/z [M + H]+ = 323) in S. coelicolor M...
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- Letter
- Published 11 Apr 2012
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Figure 1: Structure of depsipeptides szentiamide (1) [12] and xenematide (2) [8] identified in Xenorhabdus strains.
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Scheme 1: Overview of the synthetic strategy.
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Scheme 2: Synthesis of compound 1.
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Figure 2: HPLC–MS data of an XAD-extract of X. szentirmaii (a; base-peak chromatogram), the natural 1 (b; ext...
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- Full Research Paper
- Published 17 Apr 2012
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Figure 1: Cocultivation of Xanthomonas campestris pv. vesicatoria 85-10 with three fungi on different media. ...
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Figure 2: GC/MS-chromatogram (total ion current) of the headspace of X. c. pv. vesicatoria 85-10 grown in 10 ...
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Figure 3: Structures of compounds emitted by Xanthomonas campestris pv. vesicatoria 85-10. Compound labels ar...
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Scheme 1: Synthesis of 10-methylundecan-2-one (34) and 9-methylundecan-2-one (35).
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Scheme 2: Suggested biosynthesis of methylketones found in Xanthomonas campestris pv. vesicatoria 85-10.
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Figure 4: PTR–MS mass spectra of Xanthomonas campestris pv. vesicatoria 85-10 volatiles after three days of i...
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Figure 5: GC/MS analysis of volatiles emitted by Xanthomonas campestris pv. vesicatoria 85-10 grown on differ...
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Figure 6: Testing synthetic volatiles on the growth of Rhizoctonia solani. Synthetic commercially available a...
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- Review
- Published 20 Apr 2012
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Figure 1: Biphenyl and dibenzofuran phytoalexins isolated from the Pyrinae.
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Figure 2: Biphenyl and dibenzofuran concentrations determined in S. aucuparia cell cultures after treatment w...
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Figure 3: Greenhouse-grown apple shoots inoculated with the fire-blight-causing bacterium, E. amylovora.
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Figure 4: Established formation of 3,5-dihydroxybiphenyl by biphenyl synthase (BIS) [34] and proposed biosyntheti...
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Figure 5: In vitro biosynthesis of 4-hydroxycoumarin by biphenyl synthase (BIS). No formation of 2',3,5-trihy...
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- Letter
- Published 18 May 2012
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Figure 1: Structures of pseudopyronines A (1) and B (2) and natural oxazoles (3–8) as well as synthetic oxazo...
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Figure 2: MS data from strain PB22.5, which was cultivated in [U-13C] and [U-15N] medium background and LB me...
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Figure 3: All incorporated biosynthetic precursors of the oxazoles are shown in color. The nitrogen shown in ...
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- Full Research Paper
- Published 11 Jun 2012
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Scheme 1: Summary of ansamitocin biosynthesis and structure of the related ansamycin antibiotic geldanamycin (...
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Figure 1: Fermentation products, proansamitocin (2) and derivatives 7–9, of the Asm12 and Asm21-blocked (chlo...
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Scheme 2: Mutasynthetic preparation of ansamitocin derivatives 11a–h by using 3-amino-5-chlorobenzoic acid (10...
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Scheme 3: Mutasynthetic biotransformation of proansamitocin derivatives 9a and 9b with AHBA(−) mutant A. pret...
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Scheme 4: Fermentation products 14–16 of acyl transferase Asm19-blocked mutant A. pretiosum HGF059 (Δasm19) (...
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Scheme 5: Possible mechanism of deoxygenation at C-7 of proansamitocin derivatives.
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- Full Research Paper
- Published 25 Jun 2012
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Figure 1: Important metabolites in the interaction of bacteria from the Roseobacter clade with marine algae.
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Figure 2: (A) Total ion chromatogram of a headspace extract from R. pomeroyi, (B) structures of lactones rele...
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Figure 3: Mass spectra of the compounds 7–11 emitted by R. pomeroyi.
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Scheme 1: Synthesis of compounds 7–11. For these target structures the relative configurations are shown.
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Scheme 2: Enantioselective synthesis of (2R,4S)-7 and (2S,4S)-8.
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Figure 4: Enantioselective GC analyses for the assignment of the enantiomeric compositions of natural (2S,4R)-...
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- Full Research Paper
- Published 07 Aug 2012
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Figure 1: Terpenoids 1–5 present in Alloxysta victrix and cis-fused bicyclic iridoids known from other insect...
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Figure 2: 70 eV EI-mass spectrum of the iridoid X, a component of the volatile secretions of the parasitoid w...
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Figure 3: Structures and gas chromatographic retention times of trans-fused dihydronepetalactones on a conven...
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Scheme 1: Route from (S)-pulegone to the mixture of dihydronepetalactones a and b, consequently following Wol...
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Figure 4: Configuration of the dihydronepetalactone a.
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Figure 5: Route to stereochemically pure trans-fused dihydronepetalactones a–d from (R)-limonene.
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Scheme 2: Synthesis of the key compound 16. Reaction conditions: a) O3, MeOH, −50 °C (86%); b) AcOH, piperidi...
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Scheme 3: Synthesis of trans,trans-substituted dihydronepetalactone b. Reaction conditions: a) TBDMSCl, imida...
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Figure 6: Configurations of compound 24 and the dihydronepetalactone b.
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Scheme 4: Synthesis of cis,trans-substituted dihydronepetalactone c. Reaction conditions: a) Crabtree's catal...
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Figure 7: Configurations of compound 26 and the dihydronepetalactone c.
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Scheme 5: Synthesis of a 2:3 mixture of dihydronepetalactones c and d. Reaction conditions: a) (COCl)2, DMSO,...
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Scheme 6: Formal synthesis of a mixture of dihydronepetalactones a and b from (R)-limonene.
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- Published 08 Aug 2012
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Figure 1: Structures of cis- and trans-fused iridoid lactones.
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Figure 2: 70 eV EI-mass spectrum of compounds Y and Z of Alloxysta victrix.
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Figure 3: Chemical structures of all eight stereoisomers of trans-fused iridomyrmecins and their gas chromato...
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Figure 4: Strategy for the stereoselective synthesis of trans-fused iridomyrmecins A–D from (R)-limonene.
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Scheme 1: Synthesis of the trans-fused iridomyrmecins A and B. Reaction conditions and yields: a) ammonium fo...
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Figure 5: Configurations of the trans-fused iridomyrmecins A and B’.
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Scheme 2: Synthesis of the trans-fused iridomyrmecins C and D. Reaction conditions and yields: a) Crabtree's ...
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Figure 6: Configurations of the trans-fused iridomyrmecins C and D’.
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Figure 7: Volatile terpenoids in the cephalic secretion of Alloxysta victrix. For the identification of compo...
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Figure 8: Structures of iridoids from insects and plants. Absolute configurations of 19 and 20 are "educated ...
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Figure 9: Biosynthetic ways to iridoids from geraniol.
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