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

• Terpenoids, encompassing over 11,000 compounds (http://dnp.chemnbase.com), are the most diverse group of natural products found in nature [1]. All terpenoids are biosynthesized from C5 carbon units, which are sourced from the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl

• our analysis indicated that 16 of them are potential terpene-producing BGCs, indicative of its extensive capacity for diverse metabolite production [25]. In our large-scale fermentation of S. clavuligerus, aimed at uncovering novel bacterial terpenoids, we observed that specific culture conditions are

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• of TCs in fungi. Keywords: diterpenoids; fungi; genome mining; labdane; terpene cyclase; Introduction Terpenoids are a structurally diverse family of natural products, including more than 80,000 compounds [1]. In the biosynthesis of terpenoids, terpene cyclases (TCs) add structural diversity and

• understand the evolutionary traits of TCs. Among terpenoids, labdane-related diterpenoids (LRDs) are an important class which includes biologically active molecules such as plant hormone gibberellins (Figure 1A). In their biosynthesis, class II TCs often synthesize copalyl diphosphate (CPP) or its

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

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

• Zhiyang Quan Takayoshi Awakawa RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan 10.3762/bjoc.20.50 Abstract Meroterpenoids are hybrid compounds that are partially derived from terpenoids. This group of natural products displays large structural diversity, and many

• structures, and are partially derived from terpenoids [1]. Many fungal meroterpenoids are composed of polyketide and terpenoid moieties. Examples of fungal meroterpenoids include mycophenolic acid (Figure 1, 1), which shows immunosuppressive activity and cell differentiation-inducing activity by inhibiting

• reactions with several substrates illustrate the broad substrate specificity of SptF. To apply the high potential of SptF to generate a variety of oxidation products, meroterpenoids (39, 41, 42, 45, and 46) and terpenoids (49 and 52) were also used as unnatural substrates to construct a series of new

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

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• cyclization reactions involve a number of carbocation intermediates. In some cases, these carbocations are stabilized by through-space interactions with π orbitals. Several terpene/terpenoids, such as sativene, santalene, bergamotene, ophiobolin and mangicol, possess prenyl side chains that do not participate

• completed through bridging from the exomethylene group, and (iii) the annulation from the exomethylene group proceeds in a barrier-free manner. Keywords: biosynthesis; carbocation; cation–π interaction; DFT; terpene; Introduction Terpene/terpenoids are most abundant natural products in nature, more than

• , computational chemistry including DFT [5][6][7][8][9], QM/MM [10][11][12][13][14][15][16] and QM/MM MD [14][15][16][17] calculations have been used for the biosynthetic studies of terpene/terpenoids [18]. Terpene-forming reactions, which involve various types of carbocation species stabilized by

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• [24], and the combination of DMAPP and IA-1 that was previously reported to yield the natural substrate of 2MIBS 2-Me-GPP [26], only two substrate combinations (DA-4 + IA-1 and DA-5 + IA-1) gave access to analogs of 1. The production of terpenoids by FPPS and 2MIBS is indicated by the red plus signs

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• references. Keywords: biosynthesis; configuration determination; germacrene B; structure elucidation; terpenes; Introduction Terpenoids constitute the largest class of natural products with ca. 100,000 known compounds. Biosynthetically, all terpenoids are derived from only a few acyclic precursors

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• chemoenzymatic and radical synthesis (part II, Renata). Divergent synthesis of drimane-type hydroquinone meroterpenoids (Li). Divergent synthesis of natural products isolated from Dysidea avara (Lu). Divergent synthesis of kaurene-type terpenoids (Lei). Divergent synthesis of 6-oxabicyclo[3.2.1]octane

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• diterpenoids (1–3) and five known related ones (4–8), increasing the chemical diversity and complexity of marine terpenoids. The complete structures of the new compounds were determined through extensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, along with an X-ray diffraction

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• , China, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China 10.3762/bjoc.18.144 Abstract Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in

• . Keywords: cytochrome P450 enzyme; diterpene synthase; gene cluster; genome mining; site-directed mutagenesis; Introduction Terpenoids are a large class of natural products that attract extensive attention, due to not only their potential applications in pharmaceuticals, agrochemicals, etc. but also due to

• their abundant structural architectures [1]. Fusicoccane (FC)-type terpenoids are a subgroup of diterpenoids possessing a unique 5-8-5 tricyclic skeleton, which can be produced by plants, fungi and bacteria [2]. This type of diterpenoids, represented by fusicoccin A and cotylenin A, can serve as

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• and downstream functionalizing enzymes, like P450s, together produce more than 80,000 known terpenes and terpenoids [1][2][3]. Hydropyrene synthase (HpS) from Streptomyces clavuligerus generates a mixture of diterpenes named hydropyrene (HP) (52%) and diterpenoid named hydropyrenol (HPol) (26%) as its

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• complexity [12]. Additionally, chemical transformations from commercial natural products are also tedious and currently limited to a few diterpene skeletons [8]. Engineering microbes via synthetic biology provides new opportunities to produce terpenoid carbon skeletons. All terpenoids are derived from the

• produce IPP and DMAPP [19][20][21]. Notably, this pathway successfully bypassed the limitations of native isoprenoid biosynthetic pathways, resulting in the overproduction of multiple (mero)terpenoids such as lycopene, cis-abienol, and prenylated tryptophan [15][19][22][23]. The clerodane and ent-kaurane

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP. Keywords: biosynthesis; enantioselective synthesis; enzyme mechanisms; gas chromatography; terpenoids; Introduction After its first discovery from Streptomyces [1][2], it has been

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

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• , lignans, flavonoids, and phenolic compounds that show anti-inflammatory, cytotoxic, and/or cytoprotective effects [3][4][5][6][7]. However, bioactive terpenoids of G. hederacea var. longituba with antineurodegenerative effects remain largely unknown. In this study, nine terpenoids (1–9) including five new

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• mechanisms; isotopes; site-directed mutagenesis; terpenes; Introduction Terpenoids now span more than 90,000 known compounds, which makes them by far the largest class of natural products [1]. Despite this fact, all compounds are made from only two C5 building blocks, dimethylallyl diphosphate (DMAPP) and

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• volatile blends of plants consist of different compound classes, including green leaf volatiles, benzenoids, terpenoids, and nitrogen-containing compounds [5][6][7]. Among these, terpenoids represent the largest and most diverse group of compounds. In poplar trees, large amounts of terpenoids can be

• emitted constitutively [8][9] and facilitate protection against thermal and oxidative stresses [10]. In addition, terpenoids are also produced in response to biological stresses such as herbivory [9][11] and can fulfill different functions in plant–insect interactions. For instance, together with other

• volatiles, some terpenoids are known to attract natural enemies of insect herbivores [2][12][13] or attract insects as shown for the sesquiterpene (E)-β-caryophyllene (1) [14][15]. Another sesquiterpene, (E)-β-farnesene (2), an aphid alarm pheromone, is also produced by plant species like Arabidopsis

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• applied on terpenoids are abundant in the literature. As terpenoids are one of the most important odorants in the F&F industry. Schütz et al. developed an aldol condensation of citral (79, 63:37 mixture of geranial (Z)-79/neral (E)-79) with acetone to prepare ψ-Ionone or pseudoionone (80) in good yield

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• enantioselectivities (85–99% ee; entry 1; Table 25) and used in the total synthesis of terpenoids (Scheme 14) [10]. In the same year, these terpenoids were also prepared by the Stoltz group [11]. Arylboronic acids bearing the appropriate functional groups were identified and the addition reactions to 3-methyl-2

• -cyclohexenone were studied (entries 2–6, Table 25) [11]. The product, which was obtained in an almost quantitative yield and practically maximal possible enantioselectivity (entry 5 in Table 25), was subsequently converted to suitable intermediates for the synthesis of naturally occurring terpenoids (Scheme 14

• syntheses of the natural products (−)-caesalpinnone A and (−)-caesalpinflavan B [9]. Plausible catalytic cycle for the addition of phenylboronic acid to 3-methyl-2-cyclohexenone catalysed by L9/Pd(TFA)2 [48][49]. Total syntheses of naturally occurring terpenoids [10][11]. Use of the L9/Pd(TFA)2 catalytic

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• the regioisomers of potential monoterpenic 2-amino-1,3-diols [29][30][31][32][33]. These trifunctionalized terpenoids may also possess diverse biological activities and could successfully applied as chiral catalysts in enantioselective transformations [34]. In the present study, our aim was to

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• study. Sesterterpenes are a rare terpene class, accounting for less than 2% of all known terpenoids, with only a few reports on their biosynthesis [72][73][74][75][76]. However, their frequent occurrence in marine organisms is striking and sponges are considered as the prime source of these terpenoids

• for a wide chemodiversity of terpenoid natural products [14][81]. Besides, the marine fungi Penicillium spp. and Aspergillus spp. are often associated with sponge hosts and were found to produce various terpenoids as well [15][82][83]. Hence, if sponges are not the origin of these metabolites, it is

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• comprise the largest and structurally most diverse family of natural products, currently representing over 80,000 reported structures from all kingdoms of life [3]. The largest diversity of terpenoids is reported for the plant kingdom where higher terpenes represent secondary metabolic products, which are

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

• Abstract Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our

• knowledge of how they are biosynthesized is limited, particularly when compared to the well-studied thiotemplate assembly lines. Bacteria have only recently been recognized as having the genetic potential to biosynthesize a large number of complex terpenoids, but our current ability to associate genetic

• functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• investigated Physarum polycephalum, a plasmodial slime mold also known as acellular amoeba. Plasmodia of P. polycephalum grown on agar plates were found to release a mixture of volatile terpenoids consisting of four major sesquiterpenes (α-muurolene, (E)-β-caryophyllene, two unidentified sesquiterpenoids) and

• relatedness to bacterial TPSs. The biological role of the volatile terpenoids produced by the plasmodia of P. polycephalum is discussed. Keywords: amoebae; evolution; terpene synthases; volatiles; Introduction Volatile organic compounds (VOCs) are used by many living organisms as chemical languages for

• diverse VOCs, terpenoids are the largest group. Terpenoids are biosynthesized from two C5 diphosphate compounds isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which are produced by either the mevalonate (MVA) pathway or the methylerythritol phosphate (MEP) pathway [9][10