Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• only for the incorporation of one extender unit [2][3]. Although enzyme domains with various specialised catalytic functions can be found as integral part of polyketide synthases, three domain types are fundamental to their biosynthesis, resembling the same logic as observed for fatty acid biosynthesis

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• secondary metabolite biosynthetic enzymes are distant paralogs of enzymes involved in primary metabolism [63][71]. These NP biosynthetic enzymes are hypothesized to have undergone significant sequence and selectivity changes while still operating based on the same reaction mechanism (e.g., fatty acid

• biosynthesis → polyketide biosynthesis). As such, NP biosynthetic pathways utilize members of existing enzyme families that have evolved to perform new metabolic functions. Consequently, NP BGCs “borrow” genes encoding paralogs of enzymes that have their origin in primary metabolism and that have diverged into

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• starting material for an additional elongation cycle of the fatty acid biosynthesis, leading en route to 3-hydroxy- and 2-alkenoic acids and finally to 11- and 13-octadecenoic acids. While the latter free acid was not observed, 9-octadecenoic acid was also present, formed likely by action of the Δ9

Acyl-group specificity of AHL synthases involved in quorum-sensing in Roseobacter group bacteria

• Lisa Ziesche,
• Jan Rinkel,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 1309–1316, doi:10.3762/bjoc.14.112

• biosynthesis into an AHL, or are stored in a form not cleavable by the TMSH method used. These precursor acids may also originate from fatty acid degradation, a pathway that proceeds via free coenzyme A intermediates and not via acyl carrier protein-bound substrates like in the fatty acid biosynthesis. These

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• unusual, because many ethyl esters and esters derived from carboxylic acids with an odd number of carbons were found. Since the carboxylic acid portion usually derives from fatty acid biosynthesis, a process in which the C2 starter acetyl-CoA is elongated with C2 units, esters from carboxylic acids with

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• intact native megasynthase scaffold, in which overall structural properties remain preserved, while the individual active sites are adapted for embedding custom syntheses. Megasynthases – chemistry and modes of action. a) Products of PKS and FAS megasynthases. b) Reaction cycle of iterative fatty acid

• biosynthesis as performed by fatty acid synthases (FAS). Synthesis by PKS is essentially similar, except a variation in the degree of β-carbon modification, and the variation in loading and exit transferases. Modular PKS perform one cycle per module before translocating the substrate to the next module

Lipids: fatty acids and derivatives, polyketides and isoprenoids

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2017, 13, 793–794, doi:10.3762/bjoc.13.78

• African reed frog that are likely amphibian signaling compounds [1]. Sensu lato, and this is the definition relevant to this Thematic Series: lipids include all kinds of apolar (or less polar) primary and secondary metabolites, including molecules that are formed via fatty acid biosynthesis, the

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• synthases (PKSs), in a process resembling fatty acid biosynthesis by the mammalian fatty acid synthase (FAS) [8] from which the PKSs likely evolved [9]. In both cases, simple acyl-CoA building blocks are concatenated head-to-tail to construct linear chains. Several features distinguish these two pathways

• labeling at C-2, C-4, and C-10 of the macrolide ring. This result was consistent with incorporation of (2S)-methylmalonyl-CoA during the second, fifth, and sixth chain extension cycles, with inversion of configuration at the C-2 center as found for fatty acid biosynthesis (vide infra) [24]. However

• (2RS)-methylmalonyl-CoA in D2O. These labeling patterns are consistent with inversion of stereochemistry occurring in both modules 1 and 2 as in fatty acid biosynthesis without cleavage of the C-2–H bond (giving directly the D-configuration at C-2 observed in the final product), but show that an

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• [138][139]. With the exception of a few terpenoids, most tetronates are of polyketide origin, either being completely biosynthesised by a PKS or by hijacking intermediates from fatty acid biosynthesis (Figure 6). Although the larger body of tetronates is produced by Actinobacteria, they are abundant in

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• pathways such as the acyl carrier protein activation required for fatty acid biosynthesis [13][14][15][16]. In S. aureus, however, recent studies suggest that the antimicrobial activity correlates better with an inhibition of PanK, the regulatory enzyme in CoA biosynthesis in several organisms [17

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• C (57, Figure 14), which have been isolated from different Pseudomonas strains [62][63]. Compounds 55 and 56 had been initially tested positive for antimycobacterial and antiparasitic activities and both inhibited fatty acid biosynthesis [62]. The new derivative 57, possessing a longer eastern acyl

• reduced by further enzymes involved. In fatty acid biosynthesis usually a complete reductive cycle takes place, i.e., a ketoreductase (KR) generates a hydroxy group, a dehydratase (DH) reduces to an alkene double bond, and an enoyl reductase (ER) yields a completely saturated acyl-backbone. These

• as for the above mentioned α-pyrone antibiotics myxo- and corallopyronin was expected. To identify the gene corresponding to the biosynthesis of these so-called photopyrones, all ketosynthases which are not part of the usual fatty acid biosynthesis had been identified in the genome of P. luminescens

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• may not precisely follow the IUPAC rules. Review Polyketides Polyketide synthases (PKS) are multidomain enzymes that catalyze the formation of natural products via reaction steps similar to fatty acid biosynthesis, in which C2-units are fused in Claisen condensations and modified in an iterative or

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• molecular weight carboxylic acids are found widely in metabolism, often as their co-enzyme A esters, and they then undergo condensation reactions through enols or enolates to generate C–C bonds typified by the processes of long chain fatty acid biosynthesis. α-Fluorovinyl thioethers, illustrated in Figure 2

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• either ACP (acyl carrier protein) or CoA (coenzyme A) bound thioesters depending whether they originate from fatty acid biosynthesis or degradation, respectively. Due to the variability of the first substrate regarding chain length and starting unit, the different photopyrones A–H (1–8) are produced. We

• antimycobacterial and antiparasitic activity and they inhibit the fatty acid biosynthesis [29]. Natural and unnatural derivatives have also been synthesized in order to find more potent compounds [30]. We first analyzed the strain for pseudopyronine production and were able to detect three possible compounds. After

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• intermediate, putatively phloroglucinol (12) [36]. Nitrophenol 13 likely constitutes a direct biosynthetic precursor of the myxocoumarins. Upon O-acetylation of 13 with the long-chain β-keto acid building block 14, putatively recruited from fatty-acid biosynthesis, the intermediate ester 15 could undergo C–C

The volatiles of pathogenic and nonpathogenic mycobacteria and related bacteria

• Thorben Nawrath,
• Georgies F. Mgode,
• Bart Weetjens,
• Stefan H. E. Kaufmann and
• Stefan Schulz

Beilstein J. Org. Chem. 2012, 8, 290–299, doi:10.3762/bjoc.8.31

• biosynthetic class of aromatic compounds, while metabolites of the fatty-acid-biosynthesis pathway were also present. Since M. tuberculosis grown in the Sauton liquid medium produced only a few volatiles after more than 25 days, these experimental conditions are suboptimal. M. tuberculosis cultivated in the

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• for internal methyl branches in various chain positions, while the methyl ester function is derived from S-adenosyl methionine (SAM). Keywords: actinomycetes; FAMEs; fatty acid biosynthesis; GC–MS; volatiles; Introduction Lipids in general, and particularly fatty acids (FAs), belong to the most

• synthesis and is only found in very exceptional cases of fatty acid biosynthesis [9]. Due to their ability to participate in hydrogen bonds and to form stabilised dimers, carboxylic acids have relatively low vapour pressures and, therefore, high boiling points. The volatility of carboxylic acids can be

• ) methyl 4,8-dimethyldecanoate (112), and (I) methyl 4,8-dimethylundecanoate (114). The functional group increment FG(n)FAME, HP-5 MS. Mass spectra of tentatively identified methyl 4,8-dimethyldodecanoate (115) and methyl 8-ethyl-4-methyldodecanoate (116). Fatty acid biosynthesis. McLafferty fragmentation

Biosynthesis and function of secondary metabolites

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2011, 7, 1620–1621, doi:10.3762/bjoc.7.190

• polyketide and nonribosomal peptide biosynthetic machineries, which is strongly correlated with the logic of fatty acid biosynthesis as part of the primary metabolism. Insights into the mechanisms of modular polyketide and nonribosomal peptide assembly lines open up the possibility for direct modifications