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

• biosynthetic pathways for DMTs have been primarily elucidated in fungi, with identified P450s only acting on the B ring. In this study, we isolated and characterized three bacterial DMTs, namely 3β-hydroxydrimenol (2), 2α-hydroxydrimenol (3), and 3-ketodrimenol (4), from Streptomyces clavuligerus. Through

• analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria. Keywords: bacterial terpenoid; cytochrome P450s; drimane-type sesquiterpenoid; Streptomyces clavuligerus; terpenoid biosynthesis; Introduction

• associated with DMT biosynthesis have been identified in bacteria, the corresponding natural DMTs have not been discovered [17]. In this study, we isolated and characterized three drimenol congeners (2–4) from Streptomyces clavuligerus (Figure 2a). In the genome of S. clavuligerus, we identified a cav

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

• et al. applied a fluorescence-based DNA cleavage assay coupled with HiTES to Streptomyces clavuligerus and identified the steroid 11α-hydroxyprogesterone (14) as an effective elicitor and characterized 10 cryptic enediyne-derived natural products, designated clavulynes A (15) and B–J with unusual

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

• ]. (+)-δ-Cadinene synthases have been described from Gossypium arboreum [38] and Gossypium hirsutum [39], a (−)-δ-cadinene synthase was identified in Streptomyces clavuligerus [40], and (−)-γ-cadinene synthases are known from the termite associated fungus Termitomyces sp. [41] and the bacterium

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

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

• synthase (WP_093468823), S. melanosporofaciens; labdane-related diterpene synthase (WP_019525557), Streptomyces K155; iso-elsabellatriene synthase (WP_003963279), Streptomyces clavuligerus; terpene synthase (WP_046708564.1), Streptomyces europaeiscabiei; terpene synthase (WP_012394883), Myobacterium

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

• terpinyl cation has been investigated using deuterium labelling, demonstrating different stereochemical courses in the plant Salvia officinalis [8][9] and in the bacterium Streptomyces clavuligerus [10]. Also the highly unusual methylated sesquiterpene sodorifen (4) possesses a mirror plane [11] making any

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• the plant Vellozia magdalenae [6]. Recently, prehydropyrene (6) was discovered as biosynthetic intermediate towards the diterpene hydropyrene from the Gram-positive bacterium Streptomyces clavuligerus [7]. The six- and ten-membered rings of eunicellane diterpenoids can be either cis or trans fused

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• -cineol synthase from Streptomyces clavuligerus was investigated using stereospecifically deuterated substrates. In contrast to the well investigated plant enzyme from Salvia officinalis, the reaction proceeds via (S)-linalyl diphosphate and the (S)-terpinyl cation, while the final cyclisation reaction is

• reactions (reviewed in [25]). While the stereochemical course of the GPP cyclisation to 1 has been investigated for the 1,8-cineol synthase from Salvia officinalis [26][27], it is unknown for the bacterial enzyme that was recently reported from Streptomyces clavuligerus [28]. Here we describe isotopic

• cyclases are monodomain enzymes (α) [9][10][36]. Accordingly, also the 1,8-cineol synthases from Salvia officinalis and from Streptomyces clavuligerus are not related and have evolved independently. While the plant enzyme was shown to convert GPP via (R)-LPP ((R)-5) and the (R)-terpinyl cation ((R)-6) into

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• established the structure of T-muurolol (2). The absolute configuration was determined as (1R,6S,7R,10R)-(+)-T-muurolol (2) from its optical rotary power ([α]D23 = +99.4 (c 1.10, CH2Cl2)). This is the same compound as was reported from a terpene cyclase from Streptomyces clavuligerus (accession number