A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• . Krambeck Kiyoko F. Aoki-Kinoshita Nathan E. Lewis See end of main text. 10.3762/bjoc.16.215 Abstract Systems glycobiology aims to provide models and analysis tools that account for the biosynthesis, regulation, and interactions with glycoconjugates. To facilitate these methods, there is a need for a

• , cytoplasm (bacteria and archaea), or lysosome (degradation, Man-6-P dephosphorylation and lysosomal glycoprotein biosynthesis [33][34] or paucimannose recycling [35]), are important constraints on glycosylation [36], therefore, the addition of this information to the Linear Code reaction rules provides

• earliest Krambeck et al. adaptation. Some symbols are only seen in the Krambeck et al. adaptation. Besides the “ # ” as the number symbol, Krambeck et al. also uses “Gnbis” to refer to the specific structure of bisecting GN, which is “Ma3(GNb4)(...Ma6)Mb4.” Several reaction rules for N-glycan biosynthesis

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• the lack of carbohydrate-specific modelling tools have often been named as the principal causes for these issues [18]. Heterogeneity of glycoproteins Unlike protein synthesis, which is encoded in the genome and follows a clear template, glycan biosynthesis is not template-directed. A single

• glycoprotein will exist in multiple possibilities of products that can emerge from the glycan biosynthesis pathways, and these are known as glycoforms [22]. More specifically, the variation can appear in terms of which potential glycosylation sites are occupied at any time – macroheterogeneity – or variations

• in the compositions of the glycans added to specific glycosylation sites – microheterogeneity. This variation in the microheterogeneous composition patterns arises due to the competition of glycan-processing enzymes in biosynthesis pathways [23]. Implications for the structure determination of

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• important implications in terms of the N-glycans’ biosynthesis and biodegradation [29]. As an additional interesting point, we found that the folding of the (1-6) arm over the chitobiose region is completely independent of core α(1-6) fucosylation [24], with the result that core-fucosylated and non-core

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• ) [17] and violet-quinone (3) [18] (Figure 1). Similar to those natural products, the biomimetic synthesis of balsaminone A (4) and ellagic acid (5) can be attained using oxidative dimerization reactions, based on their proposed biosynthesis (Scheme 1 and Scheme 2) [19][20]. These pathways, which start

• represent the most efficient routes to these bioactive natural products to date. Selected natural products synthesized via oxidative dimerization. Proposed biosynthesis of balsaminone A (4) [19]. Proposed biosynthesis of ellagic acid (5) [20]. Previous syntheses of balsaminone A (4) [22] and ellagic acid (5

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• ][8][9]. Various lipid A derivatives have since been synthesized to dissociate endotoxic effects from beneficial immunomodulatory activities. Lipid X, 2-N;3-O-di[(R)-3-hydroxytetradecanoyl]-ᴅ-glucosamine-1-phosphate, is the naturally occurring early monosaccharide precursor of lipid A biosynthesis

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• substrate of mycobacterial galactofuranosyltransferase GlfT2 in the transition state, we evaluated these compounds by computational methods, as well as in an enzyme assay for the possible inhibition of the mycobacterial galactan biosynthesis. Our data show that despite favorable docking scores to the active

• site of GlfT2, none of these compounds serve as efficient inhibitors of the enzymes involved in the mycobacterial galactan biosynthesis. Keywords: GlfT2; molecular modeling; mycobacterium tuberculosis; synthesis; transition state inhibitors; Introduction Tuberculosis (TB) is one of the most prevalent

• targets for new antitubercular drug developments [6]. Mycobacterial galactan is synthesized by two bifunctional galactofuranosyltransferases, GlfT1 and GlfT2 (Supporting Information File 1, Figure S1). The former one initiates the galactan biosynthesis by addition of the first two Galf residues 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

• tempting to argue that the sesterterpene biosynthesis could be performed or mediated by their microbial symbionts. This further indicates a close association, interconnectedness, and probable co-evolution between microorganisms, sponges and nudibranchs [9]. D. stellata was not only found to sequester and

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

• ), and polyketide synthases (PKS). Selected Xenorhabdus and Photorhabdus mutant strains were generated applying a chemically inducible promoter in front of the suggested fabclavine (fcl) biosynthesis gene cluster (BGC), followed by the analysis of the occurring fabclavines. Subsequently, known and

• actinomycetes and myxobacteria, the genera Photorhabdus and Xenorhabdus are promising sources to discover new SMs since up to 6.5% of their overall genome sequence are associated with SM biosynthesis [5][6]. This includes antimicrobials like isopropylstilbene, xenocoumacins, amicoumacin, and several other SMs

• . budapestensis and X. szentirmaii, and a 50 kb biosynthesis gene cluster (BGC) was identified to be responsible for their formation (Figure 1) [20]. These compounds were of special interest because of their broad-spectrum bioactivity against Gram-positive and -negative bacteria, fungi, and protozoa [20][21

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

• , representing the first committed step in the biosynthesis of the next-generation anti-inflammatory drug cyclooctatin. The intracellular target of cyclooctatin is an as of yet uncharacterized lysophospholipase, which is involved in early steps of the inflammatory signaling cascade [38][39][40]. In the last

• rational biosynthesis of novel terpenes might be possible by careful design of CotB2 mutants. Future studies using multiscale techniques to model the enzyme reaction in a complete enzyme environment will allow careful evaluation of the usefulness of such active site theozyme models. Conclusion In this work

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• the looming antibiotic crisis [5]. 4-Amino-4-deoxy-ʟ-arabinose units are activated as the phosphodiester-linked undecaprenyl derivative [6], which is then transferred by the action of several Ara4N transferases (ArnT, Figure 1) [7]. The synthesis of potential inhibitors of the biosynthesis of Ara4N

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

• approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a

• has been observed in many cases that exogenous substrates can be incorporated by bacteria into biosynthesis cascades of natural products. The use of substrates which lead to nonnatural derivatives of the natural product coined the field of mutasynthesis, e.g., siderophore analogue biosynthesis by P

• synthetase (NRPS), mutasynthons often carry thioesters to mimic the natural phosphopantetheinyl conjugate [20]. For the argyrins, the Müller group identified the corresponding biosynthetic gene cluster from Cystobacter sp. SBCb004 [21], studied the biosynthesis (Figure 2) and established a heterologous

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

• 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

• development will deepen our understanding of a significant branch of biosynthesis. The biosynthetic insights gained will likely empower a greater degree of engineering proficiency for non-natural terpene biosynthetic pathways and pave the way towards the biotechnological production of high value terpenoids

• . Keywords: bacterial sesquiterpenes and diterpenes; cytochrome P450; pathway engineering; synthetic biology; terpene biosynthesis; terpene cyclase; Introduction Evolutionary diversification of terpene biosynthetic pathways has resulted in the largest and most structurally diverse class of specialized

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

• the monoterpene linalool. There were no qualitative differences in terpenoid composition at two stages of young plasmodia. To understand terpene biosynthesis, we analyzed the transcriptome and genome sequences of P. polycephalum and identified four TPS genes designated PpolyTPS1–PpolyTPS4. They share

• communication [1][2]. Rapid progress has been made in our understanding of the VOC world of microbes, especially bacteria [3][4] and fungi [5][6]. Not only the chemical diversity of microbial VOCs is continuingly to be discovered, our understanding of their biosynthesis is also growing rapidly [7][8]. Among the

• extraction temperatures. In our study, we aimed I) to determine whether P. polycephalum releases volatile terpenoids under normal growing conditions and II) to identify and characterize the genes for terpene biosynthesis in P. polycephalum. Our results will enable us to compare terpene chemistry and their

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

• : Aspergillus; biosynthesis; drimane; secondary metabolites; sesquiterpenoid; terpenes; Introduction The fungal genus Aspergillus is well recognised as a source of structurally diverse terpenoids comprising monoterpenoids [1], sesquiterpenoids [2][3][4][5], diterpenoids [6], sesterterpenoids [7][8][9

• three human cell lines. None of the compounds tested showed any activity up to 100 μg mL−1 against the Gram-negative bacterium Escherichia coli (ATCC 25922), the fungus Candida albicans (ATCC 10231) or the plant Eragrostis tef (teff). Proposed biosynthesis and gene cluster The biosynthesis of drimane

• [30]. Therefore, the drimane synthase is likely to be different from the commonly observed sesquiterpene synthase, which belongs to the class I terpene synthases. Recently, the drimane synthase AstC involved in biosynthesis of the astellolides was identified and shown to be a novel member of the

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• , Technical University of Munich (TUM), Lichtenbergstr. 4, 85748 Garching, Germany Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel 10.3762/bjoc.15.228 Abstract CotB2 catalyzes the first committed step in cyclooctatin biosynthesis of the soil bacterium Streptomyces melanosporofaciens. To

• will focus particularly on bacterial diterpene synthases, in context with other sesqui- and ditperpene synthases of bacterial, fungal and plant origin. The initial step in diterpene biosynthesis (Figure 1) is the incremental condensation of dimethylallyl diphosphate (1) and isopentylen diphosphate (2

• , fungicidal and tumorstatic effects [32]. A key player in the biosynthesis of cyclooctatin 5 is the bacterial diterpene synthase CotB2. Different research teams have investigated CotB2 by means of biochemical [30][31][38], biophysical [33][34][35], structural biology [36][37][38][39] and computational

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

• . Compound 1 showed weak growth inhibition against Saccharomyces cerevisiae. Keywords: biosynthesis; fatty acid; marine bacteria; methylation; Microbulbifer; Introduction Marine microbial symbionts are currently recognized as a reservoir of new bioactive compounds [1]. The most well-studied host animal is

• the sponge from which a vast array of natural products has been isolated and symbiotic bacteria are suggested to be responsible for the biosynthesis of such natural products [2]. Although it is well established that corals are associated with diverse microbes, coral-associated bacteria and their

• only single example of C-methylation with SAM at a carbon derived from the carbonyl carbon of acetate (C1; Figure 3D) is reported for sphingolipid biosynthesis in the yeast, Pichia pastoris [16]. SAM-dependent C-methylation takes place at the alkenyl carbon C9 of glucosylceramide, yielding a cationic

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• pyridoacridine alkaloids to be found in diverse marine sources (tunicates, sponges). Their chemistry, pharmacology and biosynthesis have been the subject of a couple of review articles [1][2][3][4]. Another source of polycyclic aromatic alkaloids are tropical plants, e.g., the Annonaceae family [5]. A very

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• adaption of the respective strains to marine conditions (see Supporting Information File 1, Tables S1 and S2 for full experimental data). With the FIND technology we managed to isolate rare fungi. To evaluate the potential for the biosynthesis of bioactive secondary metabolites we performed screenings on

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• Xiang Sun You-Sheng Cai Yujie Yuan Guangkai Bian Ziling Ye Zixin Deng Tiangang Liu Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, P. R. China 10.3762/bjoc.15.202 Abstract Sesquiterpene

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• at the nerolidyl cation (Figure 5b) [28][29][30][31]. The biosynthesis of 1–8 and 10–11 are likely to be derived from sativene with a key oxidation at C-15 followed by a Baeyer–Villiger oxidation to break the C-14–C-15 bond (Figure 5c). Based on an isotope labelling study, the γ-butyrolactone moiety

• Cochliobolus sp.) [1][26], were reported in B. sorokiniana for the first time, while, known metabolites 6 and 7 [20], 9 [34], 11 [2], and 12 [16] were previously reported from B. sorokiniana (syn. C. sativus and H. sativum). The terpene synthase responsible for the biosynthesis of the sativene/longifolene

• backbone of 1–11 remains unknown. Given that the genome of B. sorokiniana BRIP10943 has been sequenced [14], we surveyed the genome for potential terpene synthases that may be responsible for the biosynthesis of these compounds. Four putative sesquiterpene synthases were found, corresponding to the genes

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• irinans, from Physalis peruviana with highly unusual truncated backbones that resemble mammalian androstane sex hormones. Based on biomimetic chemical reactions, we propose a model that links these compounds to withanolide biosynthesis. Irinans have potent antiproliferative activities, that are however

• characteristic of Physalis species. The biosynthesis of androstanes in mammals requires three enzymatic steps starting from cholesterol (9, Figure 3B) [27]. Cholesterol (9) is converted to pregnenolone (10) by the cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), which cleaves the C20–C22 bond

• involved. While the order of oxidative steps in withanolide biosynthesis is still completely elusive [29], we propose that this fragmentation occurs at a late stage, when most typical withanolide functionalisations have already been introduced. Indeed, irinan A (2), irinan B (3) and cinedione (8) can be

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• -copaene, β-copaene, α-cubebene, β-cubebene and the bicyclic δ-cadinene were biosynthesized via (S)-(−)-germacrene D rather than via (R)-(+)-germacrene D as intermediate. Keywords: biosynthesis; deuterium labeling; germacrene; HS-SPME; terpenes; TOF–MS; Introduction The aroma profile of grape berries at

• mevalonate-dependent biosynthesis pathway (MVA) localized in the cytoplasm as well as via the mevalonate-independent 1-deoxy-ᴅ-xylulose 5-phosphate/2-C-methyl-ᴅ-erythritol 4-phosphate metabolic pathway (DOXP/MEP) localized in plastids [5]. In the MVA pathway, which was first described in yeast and animals

• leads to the formation of DMAPP and IPP, was discovered in a study focused on hopanoids [7]. Today it is known that the sesquiterpenes in Vitis vinifera are formed from FPP whose biosynthesis relies on both, the DOXP/MEP and the MVA pathway, and that they specifically accumulate in the wax layer of the

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• the first detailed analysis of the inherent atomic mobility in carbocation intermediates during sesterterpene biosynthesis. We identified two methyl groups as the least mobile of all the carbons of the carbocation intermediates in the first half of the cyclization cascade. Our analysis suggests that

• these two methyl groups are critical for the preorganization of GFPP in the biosynthetic pathways leading to sesterfisherol and quiannulatene. Keywords: biosynthesis; carbocation; DFT; substrate recognition; terpene cyclase; Introduction Terpene synthases are thought to have four main roles: (i

• 5/6/8/5 tetracyclic intermediate. This, in turn, is transformed to a 4/6-membered ring in quiannulatene biosynthesis, whereas 5/5 ring formation proceeds in sesterfisherol biosynthesis (Scheme 1, Scheme 2, and Scheme 3). Based on our DFT calculations, this regioselectivity is determined by the

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• Aromatic prenyltransferases (PTases) are enzymes that catalyze Friedel–Crafts reactions between aromatic compounds and isoprenoid diphosphates. In hapalindole biosynthesis, the aromatic PTases AmbP1 and AmbP3 exhibit surprisingly plastic selectivities. AmbP1 not only transfers the geranyl group on the C-3

• (DMATS)-type [6][7], and the membrane-bound type PTases [8][9]. Some of them exhibit broad substrate specificities and accept various aromatic compounds as prenyl acceptors. For example, NphB (also called Orf-2), the first reported ABBA-type PTase in naphtherpin biosynthesis, accepts several aromatic

• -type PTase TleC, which accepts C5 to C20 isoprenoid diphosphates in the biosynthesis of teleocidin B [11]. More interestingly, some PTases change their regiospecificity according to the chain length of the isoprenoid diphosphate, as exemplified by the DMATS-type PTase AtaPT [12]. To get knowledge about