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

• Shun Saito Midori A. Arai Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan 10.3762/bjoc.20.69 Abstract Secondary metabolites produced by actinomycete strains undoubtedly have great potential for use in applied research areas such as

• , and the associated undiscovered secondary metabolite biosynthesis genes are called “silent” genes. This review outlines several approaches to further activate the metabolic potential of actinomycetes. Keywords: actinomycete; co-culture; heat shock metabolites (HSMs); secondary metabolites; silent

• for compounds that act directly on specific molecules). Imoto and colleagues constructed a reverse screening system that targets a malignant factor of prostate cancer and thereby identified several novel compounds from actinomycete strains [16][17][18][19]. Many researchers have focused on identifying

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• actinomycetes, with 70% from Streptomyces and the rest from rare actinomycetes (non-Streptomyces) [5]. Rare actinomycetes are defined as actinomycete strains with low isolation rates when compared with the isolation of Streptomyces [6]. Currently, the discovery of new natural compounds is focusing on rare

• metabolites from the rare actinomycete Saccharopolyspora sp. KR21-0001. As a result, KR21-0001A (1), a new analog of dihydroxybenzoic acid, was discovered as a potent antioxidant. In conclusion, exploring rare actinomycetes for bioactive compound discovery represents a promising way in the quest for new drugs

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

• in Supporting Information File 1, and Table 1). We anticipated that they would be a subtype of ava-like BGCs and might produce compounds other than avenalumic acid. Among these clusters, we focused on a cluster present in the genome of a rare actinomycete, Kutzneria albida, and named it as cma

• diazo group-containing compounds through directed evolution. Finally, this study is important because of the success of genome mining for BGCs in a rare actinomycete, K. albida. Although 47 BGCs were indicated in the K. albida genome by the antiSMASH analysis, only aculeximycin was reported as a natural

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• have been reported. Here, we report on the discovery and functional characterisation of four sesquiterpene synthases from actinomycetes with novel functions, in addition to several actinomycete terpene synthases for which functional homologs have been identified before. Results and Discussion

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

• sequences of the model actinomycete Streptomyces coelicolor A3(2) [1] and the producer of the antiparasitic drug avermectin, Streptomyces avermitilis [2], were published. These index cases marked the transition from the pre- to the post-genomic era in microbial natural product (NP) research [3]. The

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• .18.166 Abstract Longicatenamides A–D are cyclic hexapeptides isolated from the combined culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B0596. Because these peptides are not detected in the monoculture broth of the actinomycete, they are key tools for understanding chemical

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• Abstract Four new phenolic siderophores were isolated from the actinomycete Nocardia altamirensis along with the known natural product amamistatin B and a putative biosynthetic shunt product. The structures of all compounds were elucidated through 1D and 2D NMR analyses as well as mass spectrometry. The

• iron-chelating properties of the retrieved metabolites were evaluated in a chrome azurol S assay. Keywords: actinomycete; amamistatin; Nocardia; siderophore; structure elucidation; Introduction Iron is known to easily interconvert between a reduced ferrous (Fe2+) and an oxidized ferric state (Fe3

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

• were weakly inhibitory against Kocuria rhizophila at MIC 100 μg/mL and none were cytotoxic against P388 at the same concentration. Keywords: Couchioplanes; prenylated tryptophan; rare actinomycete; unsaturated fatty acid; Introduction Actinomycetes, a subgroup of filamentous Gram-positive bacteria

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

• collection sites [12]. Furthermore, we found that the DSW of Sagami Bay (Pacific Ocean side of Honshu Island, Japan) contained more unknown actinomycete species than other sea areas, which eventually led to the discovery of akazamicin, a new cytotoxic aromatic polyketide from Nonomuraea [13] and akazaoxime

• actinomycete of the genus Actinomadura. We herein describe the isolation, structure determination, and biological activities of 1‒3. Results and Discussion The producing strain Actinomadura sp. AKA43 was isolated from DSW collected at a depth of −800 m in Sagami Bay, Japan. Strain AKA43 was cultured in A16

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• bacterial sesterterpenes that were recently discovered by us from the actinomycete Streptomyces mobaraensis through a genome mining approach (Figure 1) [1]. All seven compounds are produced by a canonical terpene synthase, representing the first reported sesterterpene synthase of the classical type I from

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

• -10-1 Yurigaoka, Natori, Miyagi 981-1295, Japan Department of Marine Science, Faculty of Fisheries and Marine Science, Diponegoro University, Semarang, Central Java 50275, Indonesia 10.3762/bjoc.16.222 Abstract Chemical investigation of secondary metabolites from a marine-derived actinomycete strain

• compounds are considered to be the metabolites of bacterial endosymbionts that internalized biosynthetic genes, likely to have evolved in an actinomycete or an ancestral bacterium in the same lineage. Further exploration of marine habitats has been disclosing a number of unprecedented molecules of

• actinomycete origin. For example, salinosporamide A, an antitumor drug candidate in clinical trials, is a proteasome inhibitor with an unusual γ-lactam-β-lactone bicyclic core produced by marine Salinospora tropica [10]. Abyssomicin, another example of uncommon polycyclic frameworks, is an antibacterial

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• ; tetrahydropyranes; Introduction Сhiral phosphonates [1][2] and phosphoryl-substituted heterocycles [2][3][4] have received significant attention in recent years due to their wide range of biological activity. For example, SF-2312 (1) is a natural antibiotic – an enolase inhibitor produced by the actinomycete

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• rutaceous plants [9]. Examples from microbes include chymase inhibitors SF2809-I to VI from an actinomycete of the genus Dactylosporangium [10], a quorum sensing signaling molecule 2,4-dihydroxyquinoline (DHQ, 4) from Gram-negative bacteria Pseudomonas aeruginosa and Burkholderia thailandensis, [7], and 4-O

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• species demonstrated that the distribution of secondary metabolite biosynthetic genes was not the same even in phylogenetically close species [11]. This finding became our starting point to explore the secondary metabolism in actinomycete genera from which no secondary metabolites were described. “Rare

• metabolites; the biaryl bonding between Tyr and Trp is only precedented by kistamicin A, a vancomycin-class glycopeptide produced by an actinomycete of the genus Nonomuraea (family Streptosporangiaceae) [29][30] and TMC95A–D from an ascomycetous fungus Apiospora montagnei [31]; the (E)-2,3-dehydroadipyl

• maclafungin [44], the producer of which was not identified, are metabolites of Streptomyces [33][34][35][36] or conventional rare actinomycetes [37][38]. Thus, a novel skeleton and new congeners with distinct structural features were discovered from an underexplored actinomycete of the genus Pseudosporangium

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• ), were isolated from the culture broth of an actinomycete of the genus Micrococcus, which was associated with a stony coral, Catalaphyllia sp. Their chemical structures were elucidated by spectroscopic analysis including NMR and MS, with special assistance of spin system simulation studies for the

• [18]. Herein, we report the fermentation, isolation, structure determination, and bioactivity of two new keto fatty acids, (6E,8Z)-5-oxo-6,8-tetradecadienoic acid (1) and its (6E,8E)-isomer 2, from a coral-associated actinomycete Micrococcus sp. C5-9. Results and Discussion The producing strain C5-9

• antimicrobial metabolites from an actinomycete [36] and a basidiomycete fungus [37]. In addition, long-chain saturated fatty acids possessing a keto group were detected in the solvent extract of Legionella by GC–MS analysis [38]. Fatty acid components in fresh water-derived Micrococcus species were

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• expression is the most widely used method to study complex terpenoid biosyntheses. Since many bacterial terpenoid BGCs are actinomycete-derived, terpene BGCs are often expressed in model Streptomyces hosts, such as Streptomyces albus, Streptomyces avermitilis, Streptomyces coelicolor, and Streptomyces

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• physicochemical properties that NPs typically show [3]. Abyssomicin C (AbC) is an NP with antibacterial activity that was isolated from the marine actinomycete strain Verrucosispora AB-18-032 in 2004 [4][5]. It shows antibacterial activity against Gram-positive bacteria, including resistant pathogens such as

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• -himachalene synthase produces numerous side products Apart from the recently assigned (Z)-γ-bisabolene synthase (BbS) [13], the soil-dwelling actinomycete Cryptosporangium arvum DSM 44712 also possesses a second TS gene (accession no. WP_035852539). Its encoded amino acid sequence (Figure S1, Supporting

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• the soil actinomycete Cryptosporangium arvum DSM 44712 was cloned into the E. coli expression vector pYE-express [13] (Table S1, Supporting Information File 1), because of its phylogenetic distance to characterised TSs (Figure S1, Supporting Information File 1). The amino acid sequence of the enzyme

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• and (2R,3R)-2 were found as components of antifungal and antimicrobial hexadepsipeptides called kutznerides isolated from the actinomycete Kutzneria sp. 744 [26][27]. And finally, threo-3-hydroxyglutamic acid was identified in the cell wall of Mycobacterium lacticum [28]. 4-Hydroxy-L-glutamic acid

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• -product generated during the synthesis of the antimalarial chloroquine [2]. Given this high potential for the discovery of useful chemical entities, we have recently been engaged in research regarding a family of quinolone natural products which are produced by the actinomycete Pseudonocardia sp. CL38489

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• source of inspiration for insecticides [1][2]. Among natural product-based insecticides, spinosyns are a novel kind of green insecticides with broad insecticide spectrum. Spinosyns, derivatives of bioactive substances produced by the soil actinomycete Saccharopolyspora spinosa [3], have been widely

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• in an actinomycete led to a product, which was identified as the soft coral-derived diterpene obscuronatin [25][26]. The biosynthesis of this compound can be easily rationalized via the proposed herpetopanone pathway (route b in Figure 4). Following the formation of the cyclodeca-1,5-diene

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• -butyl group. Actinomycete metabolites possessing a contiguous 1,2-diol system. Feeding experiments of 13C-labeled precursors into 1 detected by 2D-INADEQUATE NMR experiments. (a) [1,2-13C2]acetate; (b) [U-13C6]glucose. Organization of the biosynthesis gene cluster for 1. Blue, transcriptional regulator

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

• from a BAC library of S. malaysiensis DSM4137 genomic DNA as described in Supporting Information File 1, and named pYJ2. To allow the introduction of the cloned azl cluster into actinomycete host strains that are intrinsically resistant to thiostrepton (tsr), the tsr resistance cassette of pYJ2 was

• actinomycete strains. To check for significant deletions in clones housing the azl genes, PCR primer pairs were designed that would anneal approximately every 10 kbp within the gene cluster. The results were fully consistent with the whole gene cluster being present in E. coli ET12567 containing pML1. This

• widely present in actinomycete bacteria. Meanwhile, it is clear that the PKS genes in the azl cluster as sequenced are sufficient to accomplish the synthesis of the full-length azalomycin chain, without requiring any contribution from additional PKS enzymes encoded elsewhere in the S. violaceusniger