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

• polyketide portion [11][12][13][14]. One exception has been found in funiculolide biosynthesis, in which a 5-MOA-derived phthalide undergoes dearomatizing prenylation catalyzed by the UbiA-like prenyltransferase FncB (Figure 1B) [15]. In addition to prenyltransferases, transmembrane terpene cyclases play a

• 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

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

• they may be bifunctional and composed of two domains. In these enzymes a prenyltransferase domain catalyses the formation of an oligoprenyl pyrophosphate precursor from dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) that is subsequently cyclised by the terpene synthase domain

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• metabolic functions. Here, we describe a new UbiA-like prenyltransferase (Ptase) Ubi-297 encoded in a conserved operon of several bacterial taxa, including marine Flavobacteria and the genus Sacchromonospora. In silico analysis of Ubi-297 homologs indicated that members of this Ptase group are composed of

• prenyltransferase; Introduction Marine bacteria harbor an enormous potential to produce structurally diverse natural products, including prenylated aromatic metabolites [1][2]. Prenylation of metabolites most often confers increased biological activities due to enhanced lipophilicity, solubility, and improved

• cyanobacteria (Figure 3) [27]. The gene sequence eboA-E encodes five yet uncharacterized enzymes, including EboA, a putative metallo-dependent hydrolase TatD (EboB), a putative UbiA prenyltransferase (EboC), a putative 3-dehydroquinate synthase (EboD) likely catalyzing the second step in the shikimate pathway

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• downfield shifts for the carbon atoms C2 and C6, suggesting a highly delocalized positive charge in the heteroaromatic ring as depicted below. α-(Trifluoromethyl)allylcarbenium ions In 1976, Poulter et al. exploited the powerful electron-withdrawing effect of the CF3 group to elucidate the prenyltransferase

• 78 was incubated in the presence of IPP and the enzyme prenyltransferase, a rate of 5.1 × 10−4 nmol⋅min−1⋅mg−1 was measured for the condensation reaction (Scheme 24), which is to be compared to a value of 7.4 × 102 nmol⋅min−1⋅mg−1 observed for the condensation involving IPP and geranyl pyrophosphate

• (GPP). 78 was 1.5 × 106 times less reactive than geranyl pyrophosphate, allowing to conclude that the condensation mechanism involving prenyltransferase as a catalyst occurs via an ionization–condensation–elimination sequence. As suggested by the aforementioned studies, α-(trifluoromethyl)-substituted

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

• ; prenyltransferase; Introduction Aromatic prenyltransferases (PTases) catalyze Friedel–Crafts reactions between aromatic prenyl acceptors and isoprenoid diphosphate prenyl donors to construct C–C, C–O, or C–N bonds, which enrich the structural diversity of aromatic natural products [1][2]. Their reactions are

• ][20], isomerocyclases [19][21][22][23][24], and α-ketoglutarate-dependent oxygenases [25][26]. The prenyltransferase AmbP1 transfers a geranyl group onto C-3 of 1 to yield (R)-3-geranyl-3-isocyanovinylindolenine (2, Figure 2A) [20]. 2 is cyclized by isomerocyclases to give the hapalindole or

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• synthases do not comprise combinations of Class I/Class II domains but contain both a prenyltransferase domain and a terpene synthase moiety. This combination of catalytic modules allows the direct formation of the isoprenyl diphosphate substrate for the terpene synthase in a single biocatalyst. An unusual

• synthase into a sesterterpene synthase by interchanging the prenyltransferase domain. Combining these structural insights and newly created biosynthetic routes with functional expression in bacterial production hosts, industrial scale synthesis of fragrance compound (+)-sclareol, (13R)-(+)-manoyl oxide

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• scaffold as that of the ComX pheromones, but with the opposite stereochemistry [54]. The KgpA to G gene cluster was identified as encoding the kawaguchipeptins synthase in M. aeruginosa NIES-88 [55]. KgpF is a member of the ABBA prenyltransferase family, which shares a common structural motif known as the

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• prenyltransferase gene, and further genes with unknown functions. Heterologous expression of this cluster, contained in cosmid ppzOS04, in Streptomyces coelicolor M512 yielded similar phenazine compounds as formed by the wild-type producer strain, with PCA and endophenazine A as the dominant compounds, and

• prenyltransferase gene ppzP and, downstream thereof, the genes of the mevalonate pathway for supply of the isoprenoid precursor dimethylallyl diphosphate (DMAPP). Upstream of ppzP, four genes, orf1-orf4, could be identified. Database comparisons by using BLAST and Pfam searches gave no obvious clues as to whether

• alternative hypotheses may explain this observation: The regulatory gene orf3 may be involved in the regulation of the prenylation; or the deletion of the entire orf4 sequence may have affected the promoter of the prenyltransferase gene ppzP, which is situated downstream of orf4. In order to distinguish

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• to a PCP domain and reductively released by the terminal NADPH-dependent reductase domain of LtxA [49]. The indolactam ring formation further requires the activity of the P450-dependent monooxygenase/cyclase LtxB [50]. Finally, the ltx cluster encodes the aromatic prenyltransferase LtxC, which was