Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• process was inspired by the biocatalytic synthesis of aromatic polyketides by polyketide synthase from poly β-carbonyl substrates. Pyrrolidine-based organocatalyst C4 was able to promote a twofold atroposelective arene-forming 6-enolendo aldol condensation (Scheme 4). Sparr also realized a central-to

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• basis of classification. TE sequence alignment guided by NRPs grouped based on one or more of the above topological features may yield key insights. Future directions 3: Chemical structure metagenomics of type I polyketides The two largest natural product families are NRP and polyketides (PKs) [81

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• -synthesized and posttranslationally modified peptides, polyketides, alkaloids, aromatics, and terpenoids. This generation of young investigators will continue to shape the field of natural products for years to come. We pass on our greatest thanks to all the contributors to this special thematic issue. We

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• interesting biological activities. Keywords: biosynthesis; fungal metabolites; polyketides; resorcylic lactones; total synthesis; Introduction Alternariol and some of its derivatives are ubiquitous as fungal metabolites present in infested plants and in food and feed, but similarly in soil, in wallpapers

• overviews exist on mycotoxins in general [1][2][3], on selected Alternaria toxins [4][5][6][7][8][9][10][11][12], and on dibenzo-α-pyrones [13][14][15][16][17][18][19]. The current review will comprehensively deal with all naturally occurring polyketides derived from β-resorcylic acid (2,4-dihydroxybenzoic

• polyketide synthase (PKS) into account [25], since polyketides like zearalenone are synthesized by means of a type I PKS [22][26], while alternariol and its derivatives are likely to be obtained by catalysis with a PKS of type II [27] or possibly of type III [28]. However, no reliable information in this

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• , efficiency, and robustness of these biocatalysts are expected to enhance their usefulness and generality as synthetic tools. Apart from oxygenated terpenes and RiPPs, chemo-enzymatic approaches for polyketides and non-ribosomal peptides (NRPs) are considered more suitable for the second and third strategies

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• classes of natural products isolated from Microbulbifer to date include alkaloids [15], fatty acid and polyketides [16][17], and non-ribosomally synthesized peptides [3][4][7]. These findings validate the potential for secondary metabolite discovery from Microbulbifer genus. This review will cover the

• publicly available which are typically 5 Mbp in size. Computational mining these genomes with antiSMASH reveals that these bacteria, though not endowed with the biosynthetic prowess of actinomycetes, do still possess BGCs encoding NRPS-derived peptides, polyketides, RiPPs, and siderophores [4][147]. A

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• University, Hangzhou 310030, China Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China 10.3762/bjoc.20.131 Abstract Polyketides are a major class of natural products, including bioactive

• stereochemical outcomes of KRs. These updated fingerprint motifs for stereochemical prediction not only enhance our understanding of the enzymatic mechanisms governing stereocontrol but also facilitate accurate stereochemical prediction and genome mining of polyketides derived from modular cis-AT PKSs. Keywords

• : bioinformatics; conserved motifs; ketoreductase; polyketide synthase; stereocontrol; Introduction Type I modular polyketide synthases (PKSs) are large enzyme complexes that play a crucial role in the biosynthesis of bacterial polyketides, including many important clinical drugs such as erythromycin (antibiotic

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• biocatalysts, capable of catalyzing a wide range of reactions and processing a variety of substrates [35][36]. They effectively recognize different structural types, including aromatic compounds, polyketides, terpenes, peptides, and carbohydrates [37][38][39][40]. To investigate the substrate spectrum of CavA

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• (Figure 3a) [51]. Zeeck's group has successfully isolated metabolites consisting of diverse structural classes from only a few microbial species by their OSMAC approach [52][53][54]. By applying this method, Rateb et al. and Sproule et al. discovered 22-membered macrolactone polyketides designated

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

• glutamate decarboxylase, and incubated with BaeJ-KS2. Substrate binding was demonstrated through 13C NMR analysis of the products against the background of various control experiments. Keywords: bacillaene; biosynthesis; enzyme mechanisms; isotopes; trans-AT polyketide synthases; Introduction Polyketides

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• .20.66 Abstract Chemoenzymatic strategies that combine synthetic and enzymatic transformations offer efficient approaches to yield target molecules, which have been increasingly employed in the synthesis of bioactive natural products. In the biosynthesis of macrocyclic nonribosomal peptides, polyketides

• polyketides; thioesterase; Introduction Nonribosomal peptides, polyketides, and their hybrids exhibit significant diversity and a broad spectrum of bioactivities [1][2][3]. Particularly, macrocycles from these three categories of natural products are vital resources for developing pharmaceuticals and drug

• polyketides or peptides, and form an ester bond. Then, they catalyze either intramolecular macrocyclization to give macrolactones or macrolactams with attacking of internal nucleophiles (alcohols or amine), or hydrolysis to release linear acids or peptides (Scheme 1b). Although TE domains may display

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• pathway; their non-terpenoid portions can be polyketides, indole, or shikimate-derived compounds [1][2][3]. Their hybrid nature significantly contributes to their structural diversity and wide range of biological activities. Although meroterpenoids are found ubiquitously in nature, as both primary and

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• polyketides, alkaloids, sterol derivatives, terpenoids, and macrolides, with polyketides and alkaloids comprising 40% and 32% of the total, respectively. Alkaloids are a diverse group of compounds with multiple pharmacological activities, including anti-inflammatory, antibacterial, antiviral, insecticidal

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• our attention. Several meroterpenoids, alkaloids, polyketides, and sesquiterpenoids from the species displayed various biological properties including anti-inflammatory, antimicrobial, and cytotoxic activities [7][8][9]. In the present work, two rare new examples of sulfur-containing ovalicin

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• -dependent deamination pathway for the production of avenalumic acid or p-coumaric acid. Keywords: actinomycetes; avenalumic acid; biosynthesis; p-coumaric acid; polyketides; Introduction The genomes of microorganisms possess diverse biosynthetic gene clusters (BGCs) to produce natural products [1]. In

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• great structural variability such as polyketides, terpenoids, polyketide synthase–nonribosomal peptide synthetase (PKS–NRPS) alkaloids, and cytochalasins, which have been considered as taxonomic markers of the genus [7][8][9][10]. However, it is worthwhile to mention that the name Phomopsis should no

• based the comparison of their spectral data with the previously published ones. Discussion The present study describes the isolation of two previously undescribed polyketides, named 5,7-dimethylpseudopithonone (1) and 3,9-diacetylalternariol (2) along with cytochalasins and cytosporones from Diaporthe

• medicinal plant, Trema guineensis led to the isolation of seventeen secondary metabolites, including two previously undescribed polyketides, namely 5,7-dimethylpseudopithonone (1) and 3,9-diacetylalternariol (2). This study has contributed further to our knowledge of the metabolic diversity within Diaporthe

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• plate. We further identified a cytochrome P450 monooxygenase, CYP158C1, which is able to catalyze the dimerization of isoflavones. CYP158C1 can also dimerize plant-derived polyketides, such as flavonoids and stilbenes. Our work represents a unique bacterial P450 that can dimerize plant polyphenols

• explored the substrate scope of the catalyst using a variety of plant-derived polyketides (Scheme 1). The results revealed that the 5-OH substitution on isoflavone (see compound 6) was tolerable for dimerization (Figure S15, Supporting Information File 1), whereas the additional 4’-methoxyl group at the B

• , Supporting Information File 1). Other plant polyketides, such as anthraquinones 19 and 20 and phenylpropanoids 21–24, failed to be dimerized. The reaction mechanism of P450-mediated phenol dimerization is believed to involve oxidative radical–radical coupling, though other mechanisms, such as radical

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• endoperoxide containing alkaloids, terpenoids, and polyketides have been isolated from plants, animals, bacteria, fungi, and other organisms (Figure 1) [6][7]. Because of the high reactivity of the cyclic peroxide O–O bond, these compounds exhibit various biological activities [1][2][3][4][5]. For example

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• metabolite with a methyl-branched C9 unsaturated acyl chain [31]. Moreover, salinipyrones, produced by a Salinispora strain, were shown to be biosynthetic byproducts of the rosamicin polyketide synthase [32]. Though not a result from Micromonosporaceae, another example of truncated polyketides is citreodiol

• , a similarly methyl-branched unsaturated fatty acid ester, which is produced by type I polyketide synthase in a Streptomyces strain by a heterologous expression experiment [33]. These facts suggest that 1–5 could be byproducts from the biosynthesis of larger polyketides, but further investigation is

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7, Konan, Minato-ku, Tokyo 108-8477, Japan DHC Corporation, 2-7-1 Minami-Azabu, Minato-ku, Tokyo 106-8571, Japan 10.3762/bjoc.17.141 Abstract Three new tetronate-class polyketides, nomimicins B, C, and D, along with

• , an antibacterial oxime derivative from Micromonospora [14]. Along the lines of these previous studies, metabolite analysis of actinomycetes from the DSW of Sagami Bay was further conducted, and three new tetronate-class polyketides, nomimicins B (1), C (2), and D (3) were found from a rare

• medium, and the whole culture broth was extracted with 1-butanol. The extract was subjected to silica gel and ODS column chromatography, and the final purification was achieved by reversed-phase HPLC to yield two new spirotetronate polyketides, nomimicins B (1) and C (2), along with a known compound

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• ; non-ribosomal peptides; polyketides; secondary metabolism; virulence; Introduction To thrive in their natural habitats all organisms from bacteria and fungi to plants and animals need access to sufficient nutritional sources and have to defend themselves against both, competitors and predators

• molecules like non-ribosomal peptides (NRP), polyketides (PK), terpenes or indole alkaloids [10][11]. The vast majority of fungal BGCs is found in the genomes of members of the Basidiomycota and Ascomycota including the genus Penicillium in which the first BGC was identified in 1990 [12][13][14

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• the detection of the new compounds in the complex supernatants of organisms producing non-ribosomal peptides and polyketides. It has been especially useful for monitoring the incorporation

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• -3,5-dimethoxybenzene, where the longest linear sequence consists of five steps. The key reaction was a palladium-catalyzed Suzuki coupling of an aromatic boronate with a brominated resorcin derivative. Keywords: biaryls; boronates; mycotoxins; polyketides; Suzuki coupling; Introduction 5’-Methoxy-6

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• habitat [6][7]. Their secondary metabolite machinery is activated in the sea, as indicated by the isolation of enediyne antitumor antibiotics from marine invertebrates. Namenamicin [8] and the shishijimicins [9], the chalicheamicin-type enediyne polyketides, were isolated from a colonial tunicate. These

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• fungus; modified Mosher’s method; Muyocopron laterale; polyketides; Introduction Azaphilones, which are a class of fungal polyketides with diverse structures, have received growing attention due to their various biological activities, such as the inhibition of some protein–protein interactions [1][2

• [20][26], while three azaphilone-related polyketides, namely dothideomycetones A, B, and dothideomycetide A, were isolated from the CR17 fungal strain of the Dothideomycetes class (GeneBank accession number JQ867364) [27]. Furthermore, two sesquiterpenoids produced by Pithomyces chartarum