Natural products articles within Nature Communications

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  • Article
    | Open Access

    Paclitaxel is an important anticancer drug whose biosynthetic pathway reconstruction is hindered by the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, the authors tune the promoter strength for T5αH expression in Nicotiana plants to increase the levels of paclitaxel precursor taxadien-5α-ol by three-fold and reconstitute the six step early biosynthetic pathway of paclitaxel.

    • Jack Chun-Ting Liu
    • , Ricardo De La Peña
    •  & Elizabeth S. Sattely

  • Article
    | Open Access

    Ameliorating or preventing signatures of aging in humans using natural compounds is an exciting area of research. Here the authors isolate a previously unknown phytochemical from carrots which activates defence mechanisms against oxidative stress and extends lifespan in worms, and improves glucose metabolism, promotes exercise capacity, and protects from frailty at higher age in mice.

    • Carolin Thomas
    • , Reto Erni
    •  & Michael Ristow

  • Article
    | Open Access

    Type II polyketide synthases (PKSs) normally synthesize polycyclic aromatic compounds, but the potential for the synthesis of further diverse skeletons remains under investigated. Here, the authors report the discovery of the type II PKS machinery for the biosynthesis of a five-membered nonaromatic skeleton contained in the nonproteinogenic amino acid cispentacin and the plant toxin coronatine.

    • Genki Hibi
    • , Taro Shiraishi
    •  & Tomohisa Kuzuyama

  • Article
    | Open Access

    Nonribosomal peptides have diverse bioactivities and can possess unusual moieties at their C-terminus, such as polyamines. In this study, the authors identify a class of dodecapeptides glidonins that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus, elucidate their biosynthesis, and introduce the putrescine into the C-terminus of other nonribosomal peptides.

    • Hanna Chen
    • , Lin Zhong
    •  & Xiaoying Bian

  • Article
    | Open Access

    MonCI, a flavin-dependent monooxygenase, transforms all three C = C groups in the polyene substrate into epoxides during monensin A biosynthesis. Here, the authors present the structural basis for this enzyme’s regio- and stereoselective epoxidation activity.

    • Qian Wang
    • , Ning Liu
    •  & Chu-Young Kim

  • Article
    | Open Access

    Diazo compounds, such as kinamycin, are rare bioactive natural products whose assembly has been extensively studied, but the formation of the diazo group is elusive. Here, the authors report O-methyltransferase-like protein, AlpH, which is responsible for the l-glutamylhydrazine incorporation in kinamycin biosynthesis.

    • Yuchun Zhao
    • , Xiangyang Liu
    •  & Ming Jiang

  • Article
    | Open Access

    Maize has an unconventional proanthocyanidin (PA) biosynthetic pathway which produces rare stereoisomers of PA monomers and dimers, highlighting an opportunity for further improving the nutritional value of maize.

    • Nan Lu
    • , Ji Hyung Jun
    •  & Richard A. Dixon

  • Article
    | Open Access

    Diterpene synthase VenA catalyses the synthesis of venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. Here, the authors report crystal structures of apo- and holo-VenA, provide mechanistic insights into its substrate selectivity and promiscuity, and engineer VenA into a sesterterpene synthase.

    • Zhong Li
    • , Lilan Zhang
    •  & Shengying Li

  • Article
    | Open Access

    The fungal dioxygenase AsqJ catalyses the conversion of benzo[1,4]diazepine-2,5-diones into quinolone antibiotics, and can also catalyse the production of quinazolinones. Here, the authors perform comprehensive substrate promiscuity mapping of AsqJ revealing its large tolerance towards various substrates, giving biocatalytic access to a plethora of biomedically valuable heterocyclic frameworks.

    • Manuel Einsiedler
    •  & Tobias A. M. Gulder

  • Article
    | Open Access

    Cyclic peptides are important bioactive compounds and drugs, synthesised by enzymatic side-chain macrocyclization of ribosomal peptides, which rarely involves histidine residues. Here, the authors report the discovery and biosynthesis of tricyclic lanthipeptide noursin, constrained by a tri amino acid labionin crosslink and histidine-to-butyrine crosslink, which is important for copper binding of noursin.

    • Yuqing Li
    • , Yeying Ma
    •  & Huan Wang

  • Article
    | Open Access

    Diketopiperazine (DKP) natural products have diverse structures and biological functions. Here, the authors elucidate the biosynthetic pathway for indole alkaloid DKP nocardioazine B which includes DKP stereoisomerization by an unusual aspartate/glutamate racemase homolog and N- and C-methylation by a dual function methyltransferase.

    • Garrett Deletti
    • , Sajan D. Green
    •  & Amy L. Lane

  • Article
    | Open Access

    Collateral sensitivity (CS), whereby resistance to one drug is accompanied by increased sensitivity to another, provides new opportunities for antimicrobial drug discovery. Here, Liu et al. screen large chemical libraries across 29 drug-resistant E. coli strains to identify multiple CS interactions, including natural products with potent CS activities against cephalosporin-resistant strains.

    • Dennis Y. Liu
    • , Laura Phillips
    •  & Roger G. Linington

  • Article
    | Open Access

    RiPP discovery has expanded the scope of post-translational modification chemistry, but genome mining of RiPP classes remains an unsolved challenge. Here, the authors employed bioinformatics and synthetic biology approaches to discover and characterize an unknown class of RiPPs, defined by an unusual amino-modified C-terminus.

    • Hengqian Ren
    • , Shravan R. Dommaraju
    •  & Huimin Zhao

  • Article
    | Open Access

    Biosynthesis of complex polyketides by polyketide synthases often relies on trans-acting enzymes to modify the intermediates. Here, the authors elucidate how β-methylation enzymes identify their substrates. The recognition is imperfect, resulting in a doubly β-methylated virginiamycin derivative.

    • Sabrina Collin
    • , Russell J. Cox
    •  & Arnaud Gruez

  • Article
    | Open Access

    Intermodular recognition in polyketide synthase (PKS) is a key prerequisite for catalysis and assembly-line engineering. Here, the authors present a specific domain interaction between modules and an evolution-oriented strategy for PKS engineering derived from the enoylreduction module of azalomycin F.

    • Guifa Zhai
    • , Yan Zhu
    •  & Yuhui Sun

  • Article
    | Open Access

    A diterpenoid biosynthetic gene cluster (BGC) has been identified in a few species in the Lamiaceae (mint) family, but its origin and evolution remain unclear. Here, the authors report assembly of genomes of three species within the family and reveal the dynamic evolutionary trajectory of the BGC.

    • Abigail E. Bryson
    • , Emily R. Lanier
    •  & Björn Hamberger

  • Article
    | Open Access

    Comparing experimental mass spectra to reference spectra can enable natural product identification, but these spectral libraries are often incomplete and not universally applicable. Here, the authors present SNAP-MS, a tool that allows assigning compound families without experimental or calculated reference spectra.

    • Nicholas J. Morehouse
    • , Trevor N. Clark
    •  & Roger G. Linington

  • Article
    | Open Access

    The biosynthetic pathway of type II ganoderic acids (GAs) in Ganoderma lucidum, a traditional medicinal mushroom, is unknown. Here, the authors assemble the genome of type II GAs accumulating accession, identify CYPs involving in type II GAs biosynthesis, and achieve their production in engineered baker’s yeast.

    • Wei Yuan
    • , Chenjian Jiang
    •  & Han Xiao

  • Article
    | Open Access

    4(3H)-quinazolinone is the core scaffold in more than 200 natural alkaloids and numerous drugs. Here, the authors show an alternative assembly machinery for 4(3H)-quinazolinone mainly includes a two-module NRPS catalysing tripeptide formation, unusual N-3 original sources and an α-KGD catalysing the C-N bond oxidative cleavage of a tripeptide to form a dipeptide.

    • Xi-Wei Chen
    • , Li Rao
    •  & Yi Zou

  • Article
    | Open Access

    The occurrence of isomers of the bicyclic octapeptide α-amanitin, which presents a macrolactam with a tryptathionine cross-link forming a handle, has been reported under the term of atropoisomers. Here, the authors synthesize its analogs and analyse their isomers, proposing and describing for them the term ansamer.

    • Guiyang Yao
    • , Simone Kosol
    •  & Roderich D. Süssmuth

  • Article
    | Open Access

    Catalysed oxidative C-C bond formation reactions are important in the synthesis of natural products, but poorly tolerated by polyphenolic flavones. Here the authors report the reactivity of molecular oxygen in alkaline water without added catalyst for the synthesis of a collection of flavone dimers and trimers.

    • Xin Yang
    • , Sophie Hui Min Lim
    •  & Dejian Huang

  • Article
    | Open Access

    Ribosomally synthesized and post-translationally modified peptides are a source of antimicrobials. Here, the authors report a platform for the rapid evaluation and characterization of biosynthetic gene clusters that enables the identification of 30 structurally diverse modified peptides, including three showing antimicrobial activities.

    • Richard S. Ayikpoe
    • , Chengyou Shi
    •  & Huimin Zhao

  • Article
    | Open Access

    The chemical diversity of peptides from ribosomal origin is a growing field of research. Here, the authors report the discovery, genomic and biosynthetic investigations of kintamdin, a ribosomally synthesized and post-translationally modified peptides featuring a beta-enamino acid and a bis-thioether macrocyclic motif.

    • Shan Wang
    • , Sixing Lin
    •  & Hai Deng

  • Article
    | Open Access

    How triptonide is made in the medicinal plant Tripterygium wilfordii is largely unknown. Here, the authors report the identification and characterization of a suite of cytochrome P450s and show their function in catalyzing the formation of triptonide from miltriadiene in tobacco and baker’s yeast.

    • Nikolaj Lervad Hansen
    • , Louise Kjaerulff
    •  & Johan Andersen-Ranberg

  • Article
    | Open Access

    Iridoid compounds are an important class of natural products. Here, the authors report on the discovery and engineering of nepetalactol-related short chain reductases and their application for the biosynthesis of nepetalactol or nepetalactone stereoisomers, as a versatile system for the production of the iridoid natural product scaffold.

    • Néstor J. Hernández Lozada
    • , Benke Hong
    •  & Sarah E. O’Connor

  • Article
    | Open Access

    Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

    • Raphael Reher
    • , Allegra T. Aron
    •  & Daniel Petras

  • Article
    | Open Access

    The market demand for acarbose, a drug used for treatment of patients affected by type-2 diabetes, has increased. In this article, the authors report the acarbose complete biosynthetic pathway, clarifying previously unknown steps and identifying a pseudoglycosyltransferase enzyme, AcbS, a homologue of AcbI that catalyzes the formation of a non-glycosidic C-N bond.

    • Takeshi Tsunoda
    • , Arash Samadi
    •  & Taifo Mahmud

  • Article
    | Open Access

    The authors show that the N-acetyltransferase PamZ acts as a self-resistance factor disabling the antibacterial paenilamicin that is produced by the honey bee larvae pathogen Paenibacillus larvae.

    • Tam Dang
    • , Bernhard Loll
    •  & Roderich D. Süssmuth

  • Article
    | Open Access

    The ergot alkaloids are a class of natural products known for their pharmacologically privileged molecular structure that are used in the treatment of neurological ailments. Here the authors report on the production of the ergot (fungus)-derived therapeutic precursor, D-lysergic acid (DLA), in baker’s yeast.

    • Garrett Wong
    • , Li Rong Lim
    •  & Wen Shan Yew

  • Article
    | Open Access

    Nonribosomal peptide synthetases work with additional enzymes to synthesise secondary metabolites and therapeutics. Here, the authors explore bacillamide D synthesis and show the oxidase action is done while the intermediate is attached to the synthetase and replicate this with an oxidase bound synthetase for bioengineering applications.

    • Camille Marie Fortinez
    • , Kristjan Bloudoff
    •  & T. Martin Schmeing

  • Article
    | Open Access

    Cytochalasans are a large family of fungal polyketide-nonribosomal peptide hybrid natural products that exhibit important pharmaceutical activities, but the mechanism of conversion of the monocytochalasans to the polycyclic, fused analogues is unclear. Here the authors reconstitute the core backbone of the cytochalasin family and describe an oxidase that catalyzes an unusual double-bond isomerization reaction.

    • Jin-Mei Zhang
    • , Xuan Liu
    •  & Yi Zou

  • Article
    | Open Access

    Microbial DNA glycosylases associated with the biosynthesis of DNA-damaging antibiotics have evolved self-resistance for their cognate natural products. Here, the authors provide evidence that cellular self-resistance is enabled by reduced affinity of the glycosylases for the excision products of the corresponding DNA lesions.

    • Elwood A. Mullins
    • , Jonathan Dorival
    •  & Brandt F. Eichman

  • Article
    | Open Access

    Peptide secondary metabolites have a diverse range of functions. Here the authors present a method to design and screen a large library of modified peptides in E. coli against a target of interest.

    • Andrew M. King
    • , Daniel A. Anderson
    •  & Christopher A. Voigt

  • Article
    | Open Access

    Enzymes installing an intact hydropersulfide (-SSH) group into natural products have so far not been identified. Here, the authors report the characterization of an S-adenosyl methionine-dependent hydropersulfide methyltransferase (GnmP) for guangnanmycin biosynthesis, and identification of three SH domains within several NRPS-PKS assembly lines as thiocysteine lyases.

    • Song Meng
    • , Andrew D. Steele
    •  & Ben Shen

  • Article
    | Open Access

    Borosins are ribosomally encoded and posttranslationally modified peptide (RiPP) natural products featuring amide-backbone α-N-methylation. Here, the authors report the discovery and characterization of type IV borosin ‘split’ pathways encoding distinct, separate α-N-methyltransferases and precursor peptide substrates.

    • Fredarla S. Miller
    • , Kathryn K. Crone
    •  & Michael F. Freeman

  • Article
    | Open Access

    The only known animal polyketide-nonribosomal peptides, the nemamides, are biosynthesized by two megasynthetases in the canal-associated neurons (CANs) of C. elegans. Here, the authors map the biosynthetic roles of individual megasynthetase domains and identify additional enzymes in the CANs required for nemamide biosynthesis.

    • Likui Feng
    • , Matthew T. Gordon
    •  & Rebecca A. Butcher

  • Article
    | Open Access

    An efficient chassis for heterologous expression of biosynthetic gene clusters (BGCs) from Gram-negative bacteria is still unavailable. Here, the authors report rational construction of genome-reduced Burkholderials chassis to facilitate production of a class of new compounds by expressing BGC from Chitinimonas koreensis.

    • Jiaqi Liu
    • , Haibo Zhou
    •  & Xiaoying Bian

  • Article
    | Open Access

    Aurantinins are polyketides with unusual connectivities and broad antibacterial activity. Here the authors show the biosynthesis of aurantinins, which proceeds via an on-line methyl esterification at the terminus that enables the iterative chain elongations prior to condensation and cyclization.

    • Pengwei Li
    • , Meng Chen
    •  & Yihua Chen

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