Cyclic Sesquiterpene–Flavanone [4+2] Hybrids, Syzygioblanes A–C, Found in an Indonesian Traditional Medicine, “Jampu Salo” (Syzygium oblanceolatum) DOI

N. Koga,

Yohei Saito, Katsunori Miyake

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(20), P. 4302 - 4307

Published: May 10, 2024

A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally "Jampu Salo" was collected on Sulawesi Island, Indonesia. It identified Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) found for the first time Sulawesi; it previously reported only eastern Philippines Borneo. phytochemical study of S. led to isolation three unprecedented meroterpenoids, syzygioblanes A–C (1–3, respectively). These compounds might be biosynthesized through [4+2] cycloaddition various germacrane-based cyclic sesquiterpenoids with flavone desmethoxymatteucinol form spiro skeleton. The unique complex structures were elucidated by microcrystal electron diffraction analysis addition general analytical techniques such high-resolution mass spectrometry, nuclear magnetic resonance methods, infrared spectroscopy. Synchrotron X-ray calculations electronic circular dichroism spectra helped determine absolute configurations. newly isolated exhibited collateral sensitivity more strongly inhibit growth multidrug resistant tumor cell line compared chemosensitive line.

Language: Английский

Chemical Evolution of Natural Product Structure DOI Creative Commons
Michael Grigalunas, Susanne Brakmann, Herbert Waldmann

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(8), P. 3314 - 3329

Published: Feb. 21, 2022

Natural products are the result of Nature's exploration biologically relevant chemical space through evolution and an invaluable source bioactive small molecules for biology medicinal chemistry. Novel concepts discovery new compound classes based on natural product structure may enable wider space. The pseudo-natural concept merges relevance with efficient by means fragment-based development to inspire matter de novo combination fragments in unprecedented arrangements. novel scaffolds retain biological but not obtainable known biosynthetic pathways which can lead chemotypes that have unexpected or bioactivities. Herein, we cover workflow design development, highlight recent examples, discuss a cheminformatic analysis significant portion active synthetic compounds were found be products. We compare as human-made equivalent, i.e. structure.

Language: Английский

Citations

142

Biosynthesis of fungal terpenoids DOI
Pan Luo,

Jia-Hua Huang,

Jian‐Ming Lv

et al.

Natural Product Reports, Journal Year: 2024, Volume and Issue: 41(5), P. 748 - 783

Published: Jan. 1, 2024

This review covers all fungal terpenoid cyclases (TCs), including class I and II TCs as well emerging UbiA-type TCs, together with their tailoring enzymes, focusing on newly identified enzymes from 2015 to August 2023.

Language: Английский

Citations

34

Terpene synthases in disguise: enzymology, structure, and opportunities of non-canonical terpene synthases DOI
Jeffrey D. Rudolf, Chin‐Yuan Chang

Natural Product Reports, Journal Year: 2019, Volume and Issue: 37(3), P. 425 - 463

Published: Oct. 25, 2019

Twelve families of enzymes that perform terpene synthase-like reactions but do not resemble canonical synthases in sequence or structure are reviewed.

Language: Английский

Citations

136

Bacterial Diterpene Biosynthesis DOI
Jeroen S. Dickschat

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(45), P. 15964 - 15976

Published: June 11, 2019

This Minireview summarises recent developments in the biosynthesis of diterpenes by diterpene synthases bacteria. It is structured class enzyme involved first committed step towards diterpenes, starting with type I synthases, followed II enzymes and more recently discovered UbiA-related synthases. A special emphasis lies on reaction mechanisms that convert simple linear precursors through cationic cascades into structurally complex, usually polycyclic carbon skeletons multiple stereogenic centres. further main focus this a discussion how these can be unravelled. Downstream modifications to bioactive molecules are also covered.

Language: Английский

Citations

123

Enzymatic Intermolecular Hetero-Diels–Alder Reaction in the Biosynthesis of Tropolonic Sesquiterpenes DOI
Qibin Chen, Jie Gao, Cooper S. Jamieson

et al.

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(36), P. 14052 - 14056

Published: Aug. 28, 2019

Diels–Alder reactions are among the most powerful synthetic transformations to construct complex natural products. Despite that increasing of enzymatic intramolecular have been discovered, intermolecular Diels–Alderases rarely described. Here, we report an hetero-Diels–Alder reaction in biosynthesis tropolonic sesquiterpenes and functionally characterize EupfF as first fungal hetero-Diels–Alderase. We demonstrate catalyzed dehydration a hydroxymethyl-containing tropolone (5) generate reactive o-quinone methide (6) might further stereoselectively control subsequent with (1E,4E,8Z)-humulenol (8) produce enantiomerically pure neosetophomone B (1). Our results reveal biosynthetic pathway 1 expand repertoire activities cyclases.

Language: Английский

Citations

93

Strobilurin biosynthesis in Basidiomycete fungi DOI Creative Commons
Risa Nofiani, Kate M. J. de Mattos-Shipley,

Karen E. Lebe

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Sept. 20, 2018

Abstract Strobilurins from fungi are the inspiration for creation of β-methoxyacrylate class agricultural fungicides. However, molecular details biosynthesis strobilurins have remained cryptic. Here we report sequence genomes two that produce and show each contains a biosynthetic gene cluster, which encodes highly reducing polyketide synthase with very unusual C-terminal hydrolase methyltransferase domains. Expression stpks1 in Aspergillus oryzae leads to production prestrobilurin A when fermentation is supplemented benzoyl coenzyme (CoA) analogue. This enables discovery previously unobserved route CoA. Reconstruction cluster A. formation A, addition str9 encoding an FAD-dependent oxygenase key oxidative rearrangement responsible toxophore. Finally, methyltransferases required complete synthesis.

Language: Английский

Citations

92

Tropolone natural products DOI
Huijuan Guo, Dávid Roman, Christine Beemelmanns

et al.

Natural Product Reports, Journal Year: 2018, Volume and Issue: 36(8), P. 1137 - 1155

Published: Dec. 17, 2018

Covering: 2008 to 2018 This review provides a comprehensive overview of newly discovered natural products containing tropolonoid motif covering up and depicts the ecological context in which they have been isolated. has strong focus on describing different analytical tools molecular biological approaches used identify underlying biosynthetic pathways.

Language: Английский

Citations

86

Enzymatic dimerization in the biosynthetic pathway of microbial natural products DOI
Jia-Wang Liu, Anan Liu, Youcai Hu

et al.

Natural Product Reports, Journal Year: 2021, Volume and Issue: 38(8), P. 1469 - 1505

Published: Jan. 1, 2021

Cytochrome P450s, laccases, and intermolecular [4 + 2] cyclases, along with other enzymes were utilized to catalyze varied dimerization of matured natural products so as create the structural diversity complexity in microorganisms.

Language: Английский

Citations

61

Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining DOI
Chen‐Yu Chiang, M. Ohashi, Yi Tang

et al.

Natural Product Reports, Journal Year: 2022, Volume and Issue: 40(1), P. 89 - 127

Published: Sept. 20, 2022

Covering: 2010 to 2022Heterologous expression of natural product biosynthetic gene clusters (BGCs) has become a widely used tool for genome mining cryptic pathways, bottom-up investigation enzymes, and engineered biosynthesis new variants. In the field fungal products, heterologous complete pathway was first demonstrated in tenellin

Language: Английский

Citations

47

Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides DOI
Hengqian Ren, Chunshuai Huang, Yuwei Pan

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1320 - 1329

Published: March 25, 2024

Language: Английский

Citations

9