Exploring and expanding the natural chemical space of bacterial diterpenes DOI Creative Commons

Xiuting Wei,

Wenbo Ning, Caitlin A. McCadden

et al.

Published: Aug. 30, 2024

Terpenoids are the largest family of natural products but relatively rare in bacteria. Genome mining reveals wide- spread prevalence terpene synthases, enzymes responsible for constructing hydrocarbon skeletons, Using an engineered E. coli diterpene production system, we screened 334 diverse synthases from 8 phyla, 17 classes, and 83 genera bacteria found that 125 (37%) were active as synthases. Isolation structural elucidation 28 bacterial diterpenes 31 TSs revealed three new skeletons previously unseen nature, known other organisms (e.g., coral, sponge, algae) with unknown biosynthetic pathways, fungi, plants) have not been seen bacteria, stereochemical isomers diterpenes. This study will lead to novel products, advances terpenoid biosynthesis roles these products.

Language: Английский

First trans-eunicellane terpene synthase in bacteria DOI Creative Commons
Zining Li, Baofu Xu, Volga Kojasoy

et al.

Chem, Journal Year: 2023, Volume and Issue: 9(3), P. 698 - 708

Published: Jan. 2, 2023

Language: Английский

Citations

24
Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase DOI Creative Commons
Zhong Li, Lilan Zhang, Kangwei Xu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 6, 2023

Abstract Diterpene synthase VenA is responsible for assembling venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. also demonstrates substrate promiscuity by accepting geranyl pyrophosphate and farnesyl as alternative substrates. Herein, we report the crystal structures of in both apo form holo complex trinuclear magnesium cluster group. Functional structural investigations on atypical 115 DSFVSD 120 motif VenA, versus canonical Asp-rich DDXX(X)D/E, reveal that absent second Asp functionally replaced Ser116 Gln83, together bioinformatics analysis identifying hidden subclass type I microbial terpene synthases. Further analysis, multiscale computational simulations, structure-directed mutagenesis provide significant mechanistic insights into selectivity catalytic VenA. Finally, semi-rationally engineered sesterterpene to recognize larger geranylfarnesyl

Language: Английский

Citations

24
Discovery of a terpene synthase synthesizing a nearly non-flexible eunicellane reveals the basis of flexibility DOI Creative Commons
Jinfeng Li,

Chen Bao,

Zunyun Fu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 15, 2024

Abstract Eunicellane diterpenoids, containing a typical 6,10-bicycle, are bioactive compounds widely present in marine corals, but rarely found bacteria and plants. The intrinsic macrocycle exhibits innate structural flexibility resulting dynamic conformational changes. However, the mechanisms controlling remain unknown. discovery of terpene synthase, MicA, that is responsible for biosynthesis nearly non-flexible eunicellane skeleton, enable us to propose feasible theory about structures. Parallel studies all synthases nature discovered date, including 2 Z -geranylgeranyl diphosphate incubations density functional theory-based Boltzmann population computations, reveale trans -fused bicycle with -configuration alkene restricts skeleton. catalytic route enzymatic mechanism MicA also elucidated by labeling experiments, calculations, analysis artificial intelligence-based model, mutational studies.

Language: Английский

Citations

6
Exploring and expanding the natural chemical space of bacterial diterpenes DOI Creative Commons

Xiuting Wei,

Wenbo Ning, Caitlin A. McCadden

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 19, 2025

Terpenoids are the largest family of natural products but relatively rare in bacteria. Genome mining reveals widespread prevalence terpene synthases, enzymes responsible for constructing hydrocarbon skeletons, Here, we show that 125 (37%) 334 synthases from 8 phyla, 17 classes, and 83 genera bacteria active as diterpene synthases. Isolation structural elucidation 28 diterpenes 31 reveal three previously unreported skeletons other organisms with unknown biosynthetic pathways, known to best our knowledge not seen bacteria, or new stereochemical isomers diterpenes. We also identify type I myxobacteria cyanobacteria. This study will help discover products, advance studies terpenoid biosynthesis enzymology, provide model systems probe ecological roles terpenes.

Language: Английский

Citations

0
Biosynthesis, enzymology, and future of eunicellane diterpenoids DOI Creative Commons
Zining Li, Jeffrey D. Rudolf

Journal of Industrial Microbiology & Biotechnology, Journal Year: 2023, Volume and Issue: 50(1)

Published: Jan. 1, 2023

Abstract Eunicellane diterpenoids are a remarkable family of terpene natural products and have been high interest for over five decades. Widely distributed in soft corals rare plants, eunicellanes were also recently identified actinobacteria. These terpenoids foundational 6/10-bicyclic frameworks that frequently oxidized into structures containing transannular ether bridges. Interest their unique promising biological activities, such as the paclitaxel-like activities eleutherobin sarcodictyins, has led to advancements product isolation, total synthesis, medicinal chemistry, drug lead development. Until recently, however, there was little known about biosynthesis enzymology these products, but several recent studies both bacteria coral opened up field. This review summarizes eunicellane highlights future research prospects One-Sentence Summary A summary diterpenoids, structurally biologically active found coral, bacteria.

Language: Английский

Citations

8
Canonical terpene synthases in arthropods: Intraphylum gene transfer DOI Creative Commons
Xinlu Chen, John Urban,

Jens Wurlitzer

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(51)

Published: Dec. 13, 2024

Insects employ terpenoids for communication both within and between species. While terpene synthases derived from isoprenyl diphosphate synthase have been shown to catalyze terpenoid biosynthesis in some insects, canonical (TPS) commonly found plants, fungi, bacteria were previously unidentified insects. This study reveals the presence of TPS genes likely originating via horizontal gene transfer noninsect arthropods. By examining 361 insect genomes, we identified five species Sciaridae family (fungus gnats). Additionally, Collembola (springtails) Acariformes (mites) among diverse Selected enzymes Sciaridae, Collembola, display monoterpene, sesquiterpene, and/or diterpene activities. Through comprehensive protein database search phylogenetic analysis, be most closely related those Acariformes, suggesting Sciaridae. In model Bradysia coprophila , all are highly expressed adult males, a sex- developmental stage-specific role their products. The finding insects possible evolutionary origin through intraphylum arthropods sheds light on metabolic innovation

Language: Английский

Citations

2
Structure-guided product determination of the bacterial type II diterpene synthase Tpn2 DOI Creative Commons
Emma Stowell, Michelle Ehrenberger,

Ya-Lin Lin

et al.

Communications Chemistry, Journal Year: 2022, Volume and Issue: 5(1)

Published: Nov. 8, 2022

A grand challenge in terpene synthase (TS) enzymology is the ability to predict function from protein sequence. Given limited number of characterized bacterial TSs and significant sequence diversities between them their eukaryotic counterparts, this currently impossible. To contribute towards understanding sequence-structure-function relationships type II TSs, we determined structure terpentedienyl diphosphate Tpn2 Kitasatospora sp. CB02891 by X-ray crystallography made structure-guided mutants probe its mechanism. Substitution a glycine into basic residue changed product preference clerodane skeleton syn-labdane skeleton, resulting first identified TS. Understanding how single can dictate cyclization pattern Tpn2, along with detailed bioinformatics analysis sets stage for investigation functional scope discovery novel terpenoids.

Language: Английский

Citations

10
Characterization of UbiA terpene synthases with a precursor overproduction system in Escherichia coli DOI
Tyler A. Alsup,

Melvin Osei Opoku,

Jeffrey D. Rudolf

et al.

Methods in enzymology on CD-ROM/Methods in enzymology, Journal Year: 2024, Volume and Issue: unknown, P. 395 - 417

Published: Jan. 1, 2024

Language: Английский

Citations

1
Exploring and expanding the natural chemical space of bacterial diterpenes DOI Creative Commons

Xiuting Wei,

Wenbo Ning, Caitlin A. McCadden

et al.

Published: Aug. 30, 2024

Terpenoids are the largest family of natural products but relatively rare in bacteria. Genome mining reveals wide- spread prevalence terpene synthases, enzymes responsible for constructing hydrocarbon skeletons, Using an engineered E. coli diterpene production system, we screened 334 diverse synthases from 8 phyla, 17 classes, and 83 genera bacteria found that 125 (37%) were active as synthases. Isolation structural elucidation 28 bacterial diterpenes 31 TSs revealed three new skeletons previously unseen nature, known other organisms (e.g., coral, sponge, algae) with unknown biosynthetic pathways, fungi, plants) have not been seen bacteria, stereochemical isomers diterpenes. This study will lead to novel products, advances terpenoid biosynthesis roles these products.

Language: Английский

Citations

1