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

• tryptorubin (9) biosynthesis only encodes a 26 amino acid precursor peptide and a single cytochrome P450 monooxygenase [33][79], and hence it was overlooked by genome mining algorithms. On the other hand, large PKS or NRPS BGCs can be split across multiple contigs. This mosaic-like distribution of a single

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• Karan Malhotra Jakob Franke Institute of Botany, Leibniz University Hannover, Herrenhäuser Str. 2, 30419 Hannover, Germany Centre of Biomolecular Drug Research, Leibniz University Hannover, Schneiderberg 38, 30167 Hannover, Germany 10.3762/bjoc.18.135 Abstract The cytochrome P450 monooxygenase

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

• plate. We further identified a cytochrome P450 monooxygenase, CYP158C1, which is able to catalyze the dimerization of isoflavones. CYP158C1 can also dimerize plant-derived polyketides, such as flavonoids and stilbenes. Our work represents a unique bacterial P450 that can dimerize plant polyphenols

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• enantiomers of the corresponding alcohols (R)- and (S)-albaflavenol (16ab) and the epoxide 4β,5β-epoxy-2-epi-zizaan-6β-ol (18) are known oxidation products that are all made by a cytochrome P450 monooxygenase [10][29] that is genetically clustered with the epi-isozizaene synthase for the cyclisation of FPP to

• -MIB (2). First, GPP is methylated to 14 by a SAM-dependent methyltransferase, followed by a terpene synthase catalysed cyclisation through a cationic cascade to 2. Oxidation products derived from 3 by the cytochrome P450 monooxygenase that is genetically clustered with the epi-isozizaene synthase in

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

• -directed mutagenesis (indicated through wrench) of TPS (green) for product modulation or introduction of a linker-coding sequence for co-expression of P450 monooxygenase and reductase (blue and red); 4: Heterologous expression in E. coli (depicted in orange). Construction of synthetic operons and screening

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

• subsequent oxidation by the cytochrome P450 monooxygenase Ord1 yields HOMST (108), which is the starting point for the final rearrangement towards aflatoxin B1 (94) [104][105]. Consequently, the Ord1 enzyme alone catalyses the final steps towards aflatoxin B1 (94) [106]. 1.2.4 Epoxide opening: See chapter

• (165) in Scheme 24b). For thiolactomycin (165), an iteratively acting PKS module produces a tetraketide 169 that contains all backbone carbon atoms of the natural product and which is regioselectively epoxidised at the C4 and C5 carbons by the cytochrome P450 monooxygenase TlmD1 to give 170. The

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• Catharanthus roseus [40] has been cloned and heterologously expressed in baculovirus-infected insect cells [41]. This cytochrome P450 monooxygenase belonging to the CYP76B family has been demonstrated to be involved into the biosynthesis of the alkaloid secologanin, and produced 8-hydroxynerol. It should be

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• steps in monensin biosynthesis, namely hydroxylation catalysed by the P450 monooxygenase MonD and O-methylation catalysed by the methyl-transferase MonE. The corresponding genes were deleted in-frame in a monensin-overproducing strain of Streptomyces cinnamonensis. The mutants produced the expected

Biocatalytic hydroxylation of n-butane with in situ cofactor regeneration at low temperature and under normal pressure

• Svenja Staudt,
• Christina A. Müller,
• Jan Marienhagen,
• Christian Böing,
• Stefan Buchholz,
• Ulrich Schwaneberg and
• Harald Gröger

Beilstein J. Org. Chem. 2012, 8, 186–191, doi:10.3762/bjoc.8.20

• n-alkanes, which proceeds in the presence of a P450-monooxygenase advantageously at temperatures significantly below room temperature, is described. In addition, an enzymatic hydroxylation of the “liquid gas” n-butane with in situ cofactor regeneration, which does not require high-pressure

• conditions, was developed. The resulting 2-butanol was obtained as the only regioisomer, at a product concentration of 0.16 g/L. Keywords: biotransformations; cofactor regeneration; green chemistry; hydroxylation; P450-monooxygenase; Introduction The (regioselective) oxidative functionalization of

• Arnold using a P450-monooxygenase BM-3 mutant [8]. Recently, Reetz et al. reported a remarkable improvement when using a perfluoro carboxylic acid as an additive, thereby accelerating the hydroxylation as catalyzed by a P450-monooxygenase BM-3 mutant in combination with high pressure (10 bar) at 25 °C [9

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• ; P450 monooxygenase; substrate engineering; Introduction P450 monooxygenases are a ubiquitous family of enzymes found in a wide variety of organisms in all domains of life. These enzymes catalyse oxidation reactions such as hydroxylation, epoxidation, N- and O-dealkylation and heteroatom oxidation