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

• these, drimane-type sesquiterpenoids (DMTs) are distinct due to their chemical structures, which feature a decahydronaphthalene core adorned with methyl groups, mirroring the A/B rings found in labdane-derived diterpenoids [5][6] (Figure 1a). DMTs exhibit significant biological activities, such as those

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

• Fumito Sato Terutaka Sonohara Shunta Fujiki Akihiro Sugawara Yohei Morishita Taro Ozaki Teigo Asai Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan 10.3762/bjoc.20.65 Abstract Labdane-related diterpenoids (LRDs) in fungi are a pharmaceutically important, but

• 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

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

• reconstructed two-step artificial pathway efficiently produced IPP and DMAPP and thus can be used to overproduce the clerodane and ent-kaurane diterpenes in E. coli. Collecting the essential genes in the biosynthesis of terpentetriene and ent-kaurene Terpentetriene and ent-kaurene are labdane-related diterpenes

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

• , simply by rationally mutating the active-site residues. The majority of bacterial type II diterpene TCs produce bicyclic labdane, halimadane, or clerodane skeletons with different stereochemistry, levels of unsaturation, and hydroxylation patterns [124], which undergo further conversion with their

• plant sources, which led to the production of 12 novel oxidized labdane-related diterpenes [128]. Recently, commercially available monoterpenes were incubated with cell-free extracts from E. coli expressing well-studied bacterial CYPs, resulting in 27 previously unreported terpenoids (selected examples

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

• bidentate salt bridge with D111 of the aspartate-rich motif, and two salt bridges to the diphosphate moiety derived from FGGDP (Figure 3 and Figure 5). Y295 establishes hydrogen bonds to the diphosphate moiety as well as to N220 of the NSE motif (Figure 5). In the closed conformation of the labdane-related

• 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

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

• example in the biosynthesis of labdane- and clerodane type diterpenes [41]. This close collaboration is performed either in one single bifunctional enzyme containing structure motifs of both types or sets of two different monofunctional synthases of both classes [54][55]. Engineering measures can directly

• deprotonation with occasional hydration at the C8 position of the carbocation intermediate which yields hydroxylated diphosphate products [62]. MvCPS1, however, catalyzes a C9–C8 hydride shift preceding hydration resulting in the labdane-type diterpene precursor for the antidiabetic marrubiin [63]. Double

• unamenable diterpenes with labdane- and clerodane-type structures [66]. Additional findings were provided by Jia and co-workers [67], who demonstrated high substrate promiscuity of a plant and a fungal Class I diterpene synthase. This study involved general substrates of diterpene cyclases like GGPP and its