The Biosynthetic Gene Cluster for Sestermobaraenes—Discovery of a Geranylfarnesyl Diphosphate Synthase and a Multiproduct Sesterterpene Synthase from <i>Streptomyces mobaraensis</i>

Hou, Anwei; Dickschat, Jeroen S.

doi:10.1002/anie.202010084

Cited by 46 publications

(74 citation statements)

References 55 publications

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“…Next, we discuss in detail the biosynthesis of mangicol-type sesterterpenoids. Only a few C20/C25 terpenoids based on 5,11-bicyclic systems, such as ophiobolin, 34 , 35 cotylenin A, 36 and fusicoccadiene, 37 have been reported, 38 in contrast to those derived from 5,15-systems, such as quiannulatene, 5 , 39 sesterfisherol, 40 , 41 (+)-astellatene, 42 , 43 arathanadiene derivatives, sestermobaraenes, 44 and aspergildienes. 45 In the present study, IM8 was adopted as the simplest chemical model ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

DFT Study on the Biosynthesis of Verrucosane Diterpenoids and Mangicol Sesterterpenoids: Involvement of Secondary-Carbocation-Free Reaction Cascades

Sato

Takagi

et al. 2021

JACS Au

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Some experimental observations indicate that a sequential formation of secondary (2°) carbocations might be involved in some biosynthetic pathways, including those of verrucosane-type diterpenoids and mangicol-type sesterterpenoids, but it remains controversial whether or not such 2° cations are viable intermediates. Here, we performed comprehensive density functional theory calculations of these biosynthetic pathways. The results do not support previously proposed pathways/mechanisms: in particular, we find that none of the putative 2° carbocation intermediates is involved in either of the biosynthetic pathways. In verrucosane biosynthesis, the proposed 2° carbocations ( II and IV ) in the early stage are bypassed by the formation of the adjacent 3° carbocations and by unusual skeletal rearrangement reactions, and in the later stage, the putative 2° carbocation intermediates ( VI , VII , and VIII ) are not present as the proposed forms but as nonclassical structures between homoallyl and cyclopropylcarbinyl cations. In the mangicol biosynthesis, one of the two proposed 2° carbocations ( X ) is bypassed by a C–C bond-breaking reaction to generate a 3° carbocation with a C=C bond, while the other ( XI ) is bypassed by a strong hyperconjugative interaction leading to a nonclassical carbocation. We propose new biosynthetic pathways/mechanisms for the verrucosane-type diterpenoids and mangicol-type sesterterpenoids. These pathways are in good agreement with the findings of previous biosynthetic studies, including isotope-labeling experiments and byproducts analysis, and moreover can account for the biosynthesis of related terpenes.

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Section: Resultsmentioning

confidence: 99%

DFT Study on the Biosynthesis of Verrucosane Diterpenoids and Mangicol Sesterterpenoids: Involvement of Secondary-Carbocation-Free Reaction Cascades

Sato

Takagi

et al. 2021

JACS Au

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“… 6 As a result, only a few bacterial geranylfarnesyl polyprenyl synthases have been biochemically characterized, such as those involved in the biosynthesis of somaliensenes A and B, 7 atolypenes, 8 and the sestermobaraenes. 9 Marinoterpins 1 – 3 are structurally related to the aurachins, a small family of natural products bearing prenylated quinoline, 4-quinolone, or quinoline N -oxide cores. While the marinoterpins are composed of previously unknown sesterterpenoid side chains with two unusual five-membered ethers, the aurachins more commonly possess sesquiterpenoid and monoterpenoid side chains ( Figure 4 ).…”

Section: Results and Discussionmentioning

confidence: 99%

Marinoterpins A–C: Rare Linear Merosesterterpenoids from Marine-Derived Actinomycete Bacteria of the Family Streptomycetaceae

et al. 2021

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The chemical examination of two undescribed marine actinobacteria has yielded three rare merosesterterpenoids, marinoterpins A–C ( 1 – 3 , respectively). These compounds were isolated from the culture broth extracts of two marine-derived actinomycetes associated with the family Streptomycetaceae, (our strains were CNQ-253 and AJS-327). The structures of the new compounds were determined by extensive interpretation of 1D and 2D NMR, MS, and combined spectroscopic data. These compounds represent new chemical motifs, combining quinoline- N -oxides with a linear sesterterpenoid side chain. Additionally, consistent in all three metabolites is the rare occurrence of two five-ring ethers, which were derived from an apparent cyclization of methyl group carbons to adjacent hydroxy-bearing methylene groups in the sesterterpenoid side chain. Genome scanning of AJS-327 allowed for the identification of the marinoterpin ( mrt ) biosynthetic cluster, which consists of 16 open-reading frames that code for a sesterterpene pyrophosphate synthase, prenyltransferase, type II polyketide synthase, anthranilate:CoA-ligase, and several tailoring enzymes apparently responsible for installing the N -oxide and bis-tetrahydrofuran ring motifs.

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“…The 25 isotopomers of ( 13 C)-1, ( 13 C)-2, and ( 13 C)-3 were prepared enzymatically with SmTS1 from the correspondingly labelled oligoprenyl diphosphates as reported previously [1]. The compounds were obtained as mixtures that were directly analysed by GC-MS.…”

Section: Experimental Preparation Of 13 C-labelled Compounds 1-3 and mentioning

confidence: 99%

“…The sestermobaraenes A-F (1-6) and sestermobaraol (7) are a series of bacterial sesterterpenes that were recently discovered by us from the actinomycete Streptomyces mobaraensis through a genome mining approach ( Figure 1) [1]. All seven compounds are produced by a canonical terpene synthase, representing the first reported sesterterpene synthase of the classical type I from bacteria, that is characterised by an aspartate-rich motif (DDXXD) and an NSE triad (NDLXSXXXE) for binding of a trinuclear Mg 2+ cluster [2,3].…”

Section: Introductionmentioning

confidence: 99%

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

Hou

Dickschat

2020

Beilstein J. Org. Chem.

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A 13C-labelling was introduced into each individual carbon of the recently discovered sestermobaraenes by the enzymatic conversion of the correspondingly 13C-labelled isoprenyl diphosphate precursors with the sestermobaraene synthase from Streptomyces mobaraensis. The main compounds sestermobaraenes A, B, and C were analysed by gas chromatography–mass spectrometry (GC–MS), allowing for a deep mechanistic investigation of the electron impact mass spectrometry (EIMS) fragmentation reactions of these sesterterpene hydrocarbons.

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The Biosynthetic Gene Cluster for Sestermobaraenes—Discovery of a Geranylfarnesyl Diphosphate Synthase and a Multiproduct Sesterterpene Synthase from Streptomyces mobaraensis

Cited by 46 publications

References 55 publications

DFT Study on the Biosynthesis of Verrucosane Diterpenoids and Mangicol Sesterterpenoids: Involvement of Secondary-Carbocation-Free Reaction Cascades

DFT Study on the Biosynthesis of Verrucosane Diterpenoids and Mangicol Sesterterpenoids: Involvement of Secondary-Carbocation-Free Reaction Cascades

Marinoterpins A–C: Rare Linear Merosesterterpenoids from Marine-Derived Actinomycete Bacteria of the Family Streptomycetaceae

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

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