Featured
-
-
Article
| Open AccessDiscovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway
Pathogenic microbes can often attach to surfaces and form biofilms that display increased antibiotic resistance. Here, the authors characterize the biosynthesis of a new class of natural products, the cahuitamycins, that inhibit formation of biofilms by the pathogenic bacterium Acinetobacter baumannii.
- Sung Ryeol Park
- , Ashootosh Tripathi
- & David H. Sherman
-
Article
| Open AccessTotal biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli
Opiates—the gold standard for pain relief—are currently produced by extraction from opium poppies. Here the authors show that bacteria can serve as an efficient and flexible platform for the production of opiates by demonstrating the total synthesis of Thebaine and hydrocodone from stepwise fermentation in E. coli.
- Akira Nakagawa
- , Eitaro Matsumura
- & Hiromichi Minami
-
Article
| Open AccessIntegrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway
The modification of enzymes to generate desired compounds by non-natural pathways is a useful route for the production of commodity chemicals. Here, the authors show two approaches—genome mining and computational enzyme design—to generate higher alcohols from sugar.
- Wai Shun Mak
- , Stephen Tran
- & Justin B. Siegel
-
Article
| Open AccessBiosynthesis of the mycotoxin tenuazonic acid by a fungal NRPS–PKS hybrid enzyme
Tenuazonic acid is a mycotoxin produced by various plant pathogenic fungi but its biosynthetic gene is unknown to date. Here, the authors identify the tenuazonic acid biosynthetic gene encoding a protein with a unique KS domain that conducts cyclization step for tenuazonic acid release in Magnaporthe oryzae.
- Choong-Soo Yun
- , Takayuki Motoyama
- & Hiroyuki Osada
-
Article
| Open AccessA biosynthetic model of cytochrome c oxidase as an electrocatalyst for oxygen reduction
An artificial functional mimic of cytochrome coxidase is a long term research goal for the development of oxygen reduction electrocatalysts. Here, the authors use site directed mutants of myoglobin to develop an electrocatalyst for reducing oxygen to water under ambient conditions.
- Sohini Mukherjee
- , Arnab Mukherjee
- & Abhishek Dey
-
Article
| Open AccessA novel thiol-reductase activity of Arabidopsis YUC6 confers drought tolerance independently of auxin biosynthesis
YUC6 is a flavin monooxygenase required for the synthesis of the plant hormone auxin. Chaet al. discover that in Arabidopsis, this enzyme also plays a role in combatting oxidative stress independently of auxin biosynthesis, by acting as a thiol-reductase.
- Joon-Yung Cha
- , Woe-Yeon Kim
- & Dae-Jin Yun
-
Article
| Open AccessRefining the pathway of carbide insertion into the nitrogenase M-cluster
Carbide insertion plays a pivotal role in the biosynthesis of M-cluster, the cofactor of nitrogenase. Here the authors further define the pathway for interstitial carbide atom insertion, showing that the SAM-derived methyl group is transferred to a FeS precursor sulfur before hydrogen abstraction via an SN2-type reaction.
- Jared A. Wiig
- , Yilin Hu
- & Markus W. Ribbe
-
Article |
Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase
The phosphoribosyl pyrophosphate synthase PRPS2 catalyses the first step ofde novo purine nucleotide biosynthesis, and has recently been shown to couple protein and nucleotide metabolism. Zhang et al. demonstrate that PRPS2 activity is regulated by tRNA-dependent post-translational addition of arginine.
- Fangliang Zhang
- , Devang M. Patel
- & Anna Kashina
-
Article
| Open AccessIdentification of Alp1U and Lom6 as epoxy hydrolases and implications for kinamycin and lomaiviticin biosynthesis
Kinamycins, fluostatins and lomaiviticins are naturally occurring antibiotics that possess unique diazofluorene structures and exhibit potent anti-tumour activity. Here the authors identify the epoxy hydrolases in the biosynthetic pathways of kinamycins and lomaiviticins, suggesting the existence of epoxy-intermediates in their biosynthesis.
- Bin Wang
- , Fang Guo
- & Keqian Yang
-
Article
| Open AccessSalicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids
The molecular basis for heterosis, the phenomenon whereby hybrid plants show phenotypic superiority to their parents, remains poorly understood. Here, Yanget al. show that salicylic acid biosynthesis is enhanced in hybrids of Arabidopsis thalianaand correlates with heterosis for pathogen defence.
- Li Yang
- , Bosheng Li
- & Xing Wang Deng
-
Article
| Open AccessNew peptide architectures through C–H activation stapling between tryptophan–phenylalanine/tyrosine residues
Macrocyclic, constrained peptides show promise in therapeutic applications due to the stable and defined conformations that can be produced. Here, the authors report a method to form macrocyclic peptides through C–H activation on tryptophan and coupling with iodo-substituted aryl amino acids
- Lorena Mendive-Tapia
- , Sara Preciado
- & Rodolfo Lavilla
-
Article |
Protein-pyridinol thioester precursor for biosynthesis of the organometallic acyl-iron ligand in [Fe]-hydrogenase cofactor
The iron-guanylylpyridinol cofactor of [Fe]-hydrogenase is the only stable acyl-organometallic cofactor compound found in nature. Here, the authors perform a combined structural genomics and crystallography biochemical study to determine its biosynthetic origins.
- Takashi Fujishiro
- , Jörg Kahnt
- & Seigo Shima
-
Article
| Open AccessStructural basis for full-spectrum inhibition of translational functions on a tRNA synthetase
Borrelidin is an antibiotic with antimicrobial, antifungal, antimalarial and immunosuppressive activity that targets threonyl-tRNA synthetase. Here the authors show that borrelidin functions by preventing binding of all three ThrRS substrates and inducing a distinct, non-productive, conformation of the enzyme.
- Pengfei Fang
- , Xue Yu
- & Min Guo
-
Article |
Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis
Ubiquinone is a redox-active molecule that is involved in mitochondrial electron transfer. Here, Wang et al. report a mouse model that allows for temporarily controlled ubiquinone synthesis, and show that shortened lifespan associated with lack of ubiquinone can be reversed if ubiquinone biosynthesis is restored.
- Ying Wang
- , Daniella Oxer
- & Siegfried Hekimi
-
Article |
Arabidopsis ERF109 mediates cross-talk between jasmonic acid and auxin biosynthesis during lateral root formation
Jasmonic acid induces lateral root formation in Arabidopsis by promoting auxin biosynthesis. Here, Cai et al. identify a jasmonate-induced transcription factor that regulates the expression of two auxin biosynthetic enzymes revealing a molecular mechanism for hormonal cross-talk in the root.
- Xiao-Teng Cai
- , Ping Xu
- & Cheng-Bin Xiang
-
Article |
Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin
The action of iron–sulphur proteins has been found in many important biological processes. Here, the authors present a reconstituted in vitrosystem for the characterization of a ferredoxin–ferredoxin reductase pair as an electron transfer chain in the initial step of iron–sulphur protein biogenesis.
- Holger Webert
- , Sven-Andreas Freibert
- & Roland Lill
-
Article |
Retro-biosynthetic screening of a modular pathway design achieves selective route for microbial synthesis of 4-methyl-pentanol
Microbial pathways can be engineered for the sustainable production of chemical products such as transportation fuels. Here the authors design and implement a de novo biosynthetic pathway in E. colithat is capable of producing the gasoline replacement, 4-methyl-pentanol.
- Micah J. Sheppard
- , Aditya M. Kunjapur
- & Kristala L. J. Prather
-
Article |
A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites
The malaria parasite uses the methylerythritol phosphate (MEP) pathway to synthesize crucial isoprenoid metabolites. Here the authors identify and characterize a sugar phosphatase that regulates the MEP pathway by indirectly regulating the levels of isoprenoid precursors.
- Ann M. Guggisberg
- , Jooyoung Park
- & Audrey R. Odom
-
Article
| Open AccessStructure and mechanism of an intramembrane liponucleotide synthetase central for phospholipid biosynthesis
Cytidine-diphosphate diacylglycerol (CDP-DAG) is a central liponucleotide intermediate required for the biosynthesis of some phospholipids and is synthesized by CDP-DAG synthetase (Cds). Here, Liu et al. report the structure of a Cds that shows how it can accept hydrophilic and hydrophobic substrates, and suggest a mechanism that requires two metal ions.
- Xiuying Liu
- , Yan Yin
- & Zhenfeng Liu
-
Article |
An alternative pathway contributes to phenylalanine biosynthesis in plants via a cytosolic tyrosine:phenylpyruvate aminotransferase
Plants primarily synthesize phenylalanine in plastids via arogenate. Here, Yoo et al. provide evidence that petunia flowers also employ an alternative microbial-like pathway to synthesize phenylalanine that is partially localized in the cytosol and interconnected with tyrosine catabolism.
- Heejin Yoo
- , Joshua R. Widhalm
- & Natalia Dudareva
-
Article
| Open AccessVirus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection
Host–pathogen relationships can be mediated by polyvalent glycan ligand–protein interactions. Here well-defined highly valent glycodendrimeric constructs are synthesized that can mimic pathogens, and can inhibit a model of infection by the Ebola virus.
- Renato Ribeiro-Viana
- , Macarena Sánchez-Navarro
- & Benjamin G. Davis
-
Article |
Discovery of acetylene hydratase activity of the iron–sulphur protein IspH
The iron–sulphur enzyme IspH catalyses the final step of the methylerythritol phosphate isoprenoid biosynthesis pathway. Spanet al. report that IspH can hydrate acetylenes to aldehydes and ketones, in addition to its role as a 2H+/2e−reductase.
- Ingrid Span
- , Ke Wang
- & Michael Groll
-
Article |
TEMPRANILLO genes link photoperiod and gibberellin pathways to control flowering in Arabidopsis
InArabidopsis the photoperiod pathway promotes flowering in response to longer days, but during short days flowering depends on gibberellin accumulation. This study shows that TEMPRANILLO downregulation is required to induce flowering, as TEMPRANILLOgenes repress floral induction in the photoperiod and gibberellin pathways.
- Michela Osnato
- , Cristina Castillejo
- & Soraya Pelaz
-
Article
| Open AccessDraft genome sequence and genetic transformation of the oleaginous alga Nannochloropsis gaditana
Algae show much promise in the production of biofuels owing to their high photoautotrophic biomass and lipid production rates. In this study, the draft genome ofNannochloropsis gaditanaCCMP526 and a method for the transformation of this alga are reported, facilitating the investigation of lipid synthesis and biofuel production.
- Randor Radakovits
- , Robert E. Jinkerson
- & Matthew C. Posewitz
-
Article
| Open AccessConvergent evolution in biosynthesis of cyanogenic defence compounds in plants and insects
Cyanide-releasing defence systems in plants and animals are important to the evolution of plant–herbivore interactions. The authors identify the enzymes responsible for biosynthesis of cyanogenic glucosides by Six-spot Burnet moth caterpillars, which have evolved independently from the known plant pathway.
- Niels Bjerg Jensen
- , Mika Zagrobelny
- & Søren Bak