Biosynthesis of α-pyrones

• Till F. Schäberle

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

• biosynthesis of these mostly polyketide-derived structures exist, thus it is assumed that the route towards α-pyrones has been developed several times in evolution. They can be built up by the catalytic activities of the different types of polyketide synthase (PKS) systems, and especially the final ring

• . Cyclization between C-2, C-7 and C-8, C-13, as well as lactonization takes place, resulting in alternariol (17). Subsequently, a methylation and a hydroxylation reaction occur, catalyzed by the respective enzymes. Structures of phenylnannolones and of enterocin, both biosynthesized via polyketide synthase

• systems. Pyrone ring formation. Examples for the three types of PKS systems are shown in A–C. In D the mechanism catalyzed by a free-standing ketosynthase is depicted. Herein the keto–enol tautomerism is shown. A) Polyketide synthase (PKS) type I: The end part of the phenylnannolone A biosynthesis is

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• displayed negative effects on the growth of the antagonistic fungus O. minus. By genetic analysis and manipulation of the producing Streptomyces strain the respective biosynthetic gene cluster could be identified. It encodes a hybrid polyketide synthase–non-ribosomal peptide synthase (PKS–NRPS), and

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• polyketide synthase gene cluster has not been identified yet. The streptazones are relatively small compounds suggesting that they may be volatile enough to find them in the headspace above bacterial cultures, although the presence of hydrogen bond donor and acceptor sites hints to good solubility in the

• biosynthesis of the streptopyridines. PKS: polyketide synthase; red: reduction; ta: transamination; ox: oxidation; elim: elimination. Volatile compounds identified in the headspace extract of Streptomyces strain FORM5. The amounts of the compounds are given as 0–2% (x), 2–8% (xx), >8% (xxx) relative to the

Cuevaenes C–E: Three new triene carboxylic derivatives from Streptomyces sp. LZ35ΔgdmAI

• Jing-Jing Deng,
• Chun-Hua Lu,
• Yao-Yao Li,
• Shan-Ren Li and
• Yue-Mao Shen

Beilstein J. Org. Chem. 2014, 10, 858–862, doi:10.3762/bjoc.10.82

• triene structural moiety is rarely found in natural products. Streptomyces sp. LZ35 was isolated from the intertidal soil collected at Jimei, Xiamen, China [3]. An orphan type I polyketide synthase gene cluster that contains a putative chorismatase/3-hydroxybenzoate synthase gene was identified by genome

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• , United Kingdom 10.3762/bjoc.10.55 Abstract Herein, we describe the syntheses of a complex biosynthesis-intermediate analogue of the potent antitumor polyketide borrelidin and of reference molecules to determine the stereoselectivity of the dehydratase of borrelidin polyketide synthase module 3. The

• position 12 in 1 is installed by the dehydratase of polyketide synthase (PKS) module 3 (BorDH3). Characteristic residues in the active site of the preceding ketoreductase point towards a 3D configuration of the BorDH3 precursor 3 [10][11]. Furthermore, we have shown in a previous study that BorDH3

• processes. Our aim was to assay the stereochemical course of the dehydratase of polyketide synthase (PKS) module 3 (BorDH3) in vitro. Therefore, the surrogate 5a for BorDH3 as well as reference molecules such as 6a and 6b and the corresponding methyl esters 7a and 7b, which resemble the potential assay

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• ]. In the present case, 1 is loaded on the starter module of the polyketide synthase (Scheme 1). The last PKS module releases and cyclizes seco-proansamitocin, likely by an ansamycin amide synthase (gene asm9) [23][24][25][26][27], that generates the 19-membered macrocyclic lactam proansamitocin (2

• polyketide synthase in A. pretiosum and thus no formation of new ansamitocin derivatives was encountered in these cases. In contrast, benzoic acid 11 provided Br-F-ansamitocin derivatives 21a–d after being fed to a growing culture of the mutant strain as judged by HRMS (Scheme 4). The retention times in LC

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• for the key role of late-stage hydroxylation at C-26 of the monensin molecule. Like other polyether ionophores, monensin is assembled by the polyketide biosynthetic pathway on a modular polyketide synthase (PKS) multienzyme [14]. A model has been proposed [14] for monensin biosynthesis in which an

• (5) and (d) the overlay of 5 (blue) with sodium monensin (1) (green). The proposed pathway for monensin biosynthesis in Streptomyces cinnamonensis. The polyketide synthase (PKS) initially produces an enzyme-bound triene, which is transferred to a discrete acylcarrier protein (ACPX) to give 2. After

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• . Biosynthesis of the antimycin dilactone core Antimycins are produced by a hybrid non-ribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) assembly line for which the complete biosynthetic pathway has been proposed [25][34] (Figure 3). The biosynthesis of antimycins involves the activities of fourteen

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• B (52) as a model system [51][52][53][54][55]. It was hypothesized that the carbon backbone, which is connected to an amino acid, most likely originates from a polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid machinery [56]. The discovery of a gene locus for a PKS-NRPS

• basis of the structural similarity between 208 and marinopyrrole A, another secondary metabolite derived from a marine Streptomyces species [156]. The common biosynthetic precursor 206 stems from a mixed nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) pathway. The amino acid proline is

• first oxidized and chlorinated by an FADH2-dependent halogenase to give 205, which after extension by the polyketide synthase gives the polyketides 206 and 207, respectively. The intermolecular condensation of these two components yields chlorizidine A (208) [155]. Anthraquinone-type alkaloids

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme

• A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity. One requirement for this endeavor is the supplementation of

• methylmalonate is studied and quantified, showing a surprisingly high and transferable activity of these polyketide synthase substrate analogues in vivo. Keywords: biosynthesis; coenzyme A; malonic acid; polyketide; polyketide synthase; Introduction Polyketides are ubiquitous natural products and find

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• multienzymes are responsible for setting up the complete carbon backbone of both ansamycin antibiotics [21][22][23][24]. More precisely, the biosynthesis of ansamitocins relies on a type I modular polyketide synthase (PKS), with 3-amino-5-hydroxybenzoic acid (1, AHBA) [20] as the starter unit followed by chain

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• protein or polyketide synthase or nonribosomal peptide synthetase) bound. Supporting Information Supporting Information File 114: General experimental procedures, isolation of the strain and taxonomic identification, cultivation and extraction, isolation, labeling experiments, synthesis, bioactivity

Phytoalexins of the Pyrinae: Biphenyls and dibenzofurans

• Cornelia Chizzali and
• Ludger Beerhues

Beilstein J. Org. Chem. 2012, 8, 613–620, doi:10.3762/bjoc.8.68

• pathways. Elicitor-treated cell cultures of Sorbus aucuparia served as a model system for studying phytoalexin metabolism. The key enzyme that forms the carbon skeleton is biphenyl synthase. The starter substrate for this type-III polyketide synthase is benzoyl-CoA. In apples, biphenyl synthase is encoded

• ]. Biosynthesis of biphenyls and dibenzofurans The key enzyme of the biosynthetic pathway is biphenyl synthase (BIS) [22]. This type-III polyketide synthase (PKS) catalyzes the iterative condensation of benzoyl-CoA with three acetyl units from the decarboxylation of malonyl-CoA to form a linear tetraketide

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways and highlight the unique enzyme mechanisms that were elucidated or can be anticipated for the individual products. We further include ribosomal natural products and UV-absorbing pigments from cyanobacteria. Mechanistic insights

• assumed to be the starter of polyketide chain assembly at the polyketide synthase AnaE [38]. The following polyketide extension step is predicted to be catalyzed by the polyketide synthase AnaF. The predicted protein ORF1 that is encoded in direct proximity of the ana cluster is expected to catalyze a

• Claisen-type cyclization step to form the characteristic bicyclic ring structure of anatoxin while the growing chain is tethered to the AnaF ACP domain. Experimental evidence for this suggestion is currently lacking. Finally, the bicyclic thioester is suggested to be transferred to the polyketide synthase