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

• -acyltransferase polyketide synthase biosynthetic gene cluster sdl (80 kb) from Streptomyces sp. B59 was cloned and transferred into a heterologous host, Streptomyces albus J1074, resulting in the production of a class of polycyclic macrolide shuangdaolides A (1), B, and D and dumulmycin (2) [29]. Furthermore

• , genome mining of the marine actinomycete Streptomyces seoulensis A01 enabled the identification of a giant type I polyketide synthase gene cluster (asm) [30]. Heterologous expression of the cryptic asm cluster using a bacterial artificial chromosome vector in a heterologous host led to the production of

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

• second ketosynthase of the polyketide synthase BaeJ involved in bacillaene biosynthesis (BaeJ-KS2). For this purpose, both enantiomers of a 13C-labelled N-acetylcysteamine thioester (SNAC ester) surrogate of the proposed natural intermediate of BaeJ-KS2 were synthesised, including an enzymatic step with

• compound is made through a trans-AT polyketide synthase–non-ribosomal peptide synthase (PKS-NRPS) hybrid [9][10]. Instead of using the classical domain organisation KS-AT-ACP with AT domains integrated into the PKS, trans-AT PKSs utilize discrete ATs that are not an integral part of the PKS, but rather

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• draft genome sequence of the H002 strain identified the variochelin biosynthetic gene cluster (var), which encodes PKS (polyketide synthase) and NRPS (non-ribosomal peptide synthetase) genes. Finally, the siderophores isolated in this study exhibited antibacterial activity against several bacteria

• in Supporting Information File 1). To investigate whether the identified var biosynthetic gene cluster is responsible for variochelin production, we substituted varG encoding the polyketide synthase (PKS) module with a chloramphenicol resistance (cmR) gene cassette, using homologous recombination

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

• cyclases responsible for DMOA-derived compounds. To achieve this goal, we first aimed to establish a production system for the 4-desmethyl analogue of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester by utilizing the polyketide synthase FncE, the prenyltransferase FncB, the O-methyltransferase InsA1, and the FAD

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• metabolic genes for ease of gene transfer and high substance production capabilities [10][11]. The expression of trt4 (polyketide synthase, PKS), trt2 (prenyltransferase, PT), trt5 (methyltransferase, MT), trt8 (flavin-dependent monooxygenase, FMO), and trt1 (meroterpenoid cyclase, CYC) in A. oryzae NSAR1

• pathways Furthermore, there are examples of the enzymatic synthesis of plant-derived pharmaceutical meroterpenoids through the heterologous expression of a combination of fungal and plant biosynthetic enzymes. The biosynthetic enzymes StbA (polyketide synthase, PKS) and StbC (prenyltransferase, PT) from

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

• reaction enabled us to perform a kinetic analysis of AvaA7, which confirmed that AvaA7 catalyzes the denitrification of 3-diazoavenalumic acid in avenalumic acid biosynthesis. This study deepened our understanding of the highly reducing type II polyketide synthase system as well as the diazotization

• biosynthetic pathway [13]. In this pathway, 3-amino-4-hydroxybenzoic acid (3,4-AHBA, 1), synthesized by AvaH and AvaI, is loaded onto AvaA3 (carrier protein) by AvaA1 (AMP-dependent ligase), resulting in 3,4-AHBA-AvaA3. A highly reducing type II polyketide synthase (PKS) system [15][16] (AvaA2, A4, A5, and A8

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

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• -AT, [3][4]) polyketide synthase (PKS) and non-ribosomal peptide synthase (NRPS) [2] with a dehydrating bimodule [5][6] involved in the installation of the remaining Z-configured double bond within the polyketide backbone [7]. Furthermore, a cytochrome P450 monooxygenase was recently shown to be

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

• clustered into the CYP158 clade that reportedly catalyzes dimerization of type III polyketide synthase (T3PKS) products, such as naphthols. Considering the similar biosynthetic pathway of isoflavones shared, this enzyme was expressed in E. coli and purified for in vitro biochemical assay together with four

• . Interestingly, we found that CYP158C1 clusters together with a T3PKS gene in the S. cattleya genome, which is similar to the biflaviolin [30] and naringenin [31] biosynthetic gene clusters. The native function of these type-III polyketide synthase products is believed to be involved in the protection of the

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

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

• of its biosynthesis are well established: the 19 kb gene cluster contains 6 genes and lies downstream of the conidiation pathway. The polyketide synthase PksP combines the starter units acetyl-CoA and malonyl-CoA into the heptaketide naphthopyrone YWA1 (11). The hydrolytic activity of Ayg1 shortens

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

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

• genomic information suggests the presence of biosynthetic genes for nonribosomal peptide synthetase and type III polyketide synthase in some Kocuria strains [18], which leaves a hope for new secondary metabolites. At present, only a few limited structural types of metabolites, including polyamine-derived

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• ]. Fabclavines are hexapeptide/polyketide hybrids derived from nonribosomal peptide synthetases (NRPS) and a polyketide synthase (PKS), which are connected to an unusual polyamine derived from polyunsaturated fatty acid (PUFA) synthases [20]. Beside full-length fabclavines, also shortened derivatives were

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• . aeruginosa [18]. Biotechnological engineering of producer strains aims to shutdown the natural substrate production and thereby increase the usually poor yields of the mutasynthesis products [19][20]. For bacterial natural products that originate from a polyketide synthase (PKS) or a nonribosomal peptide

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• side chains present in the (iso)nanangenines could be derived either from a fatty acid synthase (FAS) or polyketide synthase (PKS). For example, in aflatoxin biosynthesis, the hexanoyl started unit is supplied by a FAS [31], while in the meroterpenoid fumagillin biosynthesis, the unsaturated acyl chain

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• intermediate, from which deprotonation occurs at C9 to give an internal olefin (Scheme 1). In the case of 1, methylation at the C3 carbon is inconsistent with the regular methylation pattern that occurs in fatty acids synthesized by the FAS (fatty acid synthase) or polyketides from the PKS (polyketide synthase

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• (methyl-2H3)methionine. While the methylation pattern of the alternative structure 24c is difficult to understand via a polyketide biosynthesis mechanism, the formation of the assigned structure of 24 by a polyketide synthase (PKS) can be easily rationalised (Scheme 2). The acetate starter unit, bound to

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• is shown in Scheme 7 that is likely performed by a typical fungal iterative polyketide synthase (PKS). Starting from acyl-carrier-protein (ACP) bound acetate a first elongation step with malonyl-SCoA (Mal-SCoA) catalysed by an acyl transferase (AT) and a ketosynthase (KS) domain yields acetoacetyl

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• as donor, efficiently converted mediomycin B to mediomycin A in vitro. Thus, in the final steps of mediomycin A biosynthesis deamidination and sulfotransfer can take place in either order. Keywords: amidinohydrolase; clethramycin; mediomycin; polyketide synthase; sulfotransferase; Introduction

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• microorganism as a promising source of natural products. Genes for nonribosomal peptide synthetases (NRPSs) were found to be preponderant, either solely or organised in combination with polyketide synthase (PKS) genes, representing four and five clusters, respectively. Two PKS and three putative bacteriocin

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• produced azalomycin, showing that the polyketide synthase genes in the sequenced cluster are sufficient to accomplish formation of the full-length polyketide chain. This provides strong support for module iteration in the azalomycin and kanchanamycin biosynthetic pathways. In contrast, re-sequencing of the

• gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm. Keywords: colinearity; ebelactone; enzyme catalysis

• ; marginolactone; natural products; polyketide synthase; Introduction Bacterial modular Type I polyketide synthases (PKSs) are multienzymes that govern the biosynthesis of diverse complex polyketide natural products, including clinically useful antibiotics, immunosuppressants, and antitumor compounds. They follow

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

• enzymatic units that introduce nitrogen, we expanded the scope of this article to those products of polyketide synthase–non ribosomal peptide synthetase (NRPS) hybrid systems in which the polyketide portion strongly dominates the overall structure and in which the amino acid nitrogens are incorporated into

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• reaction [109][110]. The althiomycin biosynthetic gene cluster was recently identified in M. xanthus DK897 by a combination of retrobiosynthetic analysis and gene inactivation [111]. Two open reading frames (ORFs) encoding for a nonribosomal peptide synthetase (NRPS) and a NRPS/polyketide synthase (PKS