目次

Editorials

ヨーロッパ全体で科学研究を標準化し、境界をなくすという考えは非常に単純だが、実現は簡単ではなく、優先的な取り組みが必要だ。

Science without borders p.5

The idea of standardizing science and removing barriers to research mobility across Europe is simple, but putting it into practice has proved more challenging.

doi: 10.1038/502005a

行動遺伝学者は、自らの研究が誤って解釈されるのを防ぐため、慎重に行動すべきだ。

Dangerous work p.5

Behavioural geneticists must tread carefully to prevent their research being misinterpreted.

doi: 10.1038/502005b

科学者は、研究の意義や有用性を、ソーシャルメディアなどを使って直接社会に分かりやすく伝える工夫をすべきだ。

Cross the road p.6

Research on chickens is legitimate — but scientists and funders must learn to justify it.

doi: 10.1038/502006a

News

米政府機関の一部閉鎖で、科学界にも影響が。

US government shuts down p.13

Research disrupted as lawmakers spar over funding.

doi: 10.1038/502013a

米アリゾナ州で行われる掘削調査で、三畳紀の姿がより詳しく明らかになると、期待が。

Geologists take drill to Triassic park p.14

Arizona rock core to yield coherent picture of turbulent period.

doi: 10.1038/502014a

オーストラリアの新しい保守政権が打ち出した環境政策や科学政策に、科学界から苛立ちが。

Overhauls set scientists on edge p.15

Australian government axes carbon tax and designated science minister, but says it will not cut research funding.

doi: 10.1038/502015a

臨床試験に絡んだ不正行為で有罪判決を受けた米国の製薬会社元トップが、最高裁へ上訴。

Uncertainty on trial p.17

Former US drug-company chief appeals conviction for fraud over interpretation of results.

doi: 10.1038/502017a

理論物理学者たちが、さまざまな計算を駆使して、粒子の相互作用について新たな見方を。

Rethinking particle dynamics p.19

Theoretical physicists are pursuing competing ways to calculate how particles interact.

doi: 10.1038/502019a

多くの製薬会社が新薬の優先審査、ブレークスルー治療認定を目指しているが、その定義には不明瞭な点も。

Pharma scrambles to fast-track drugs p.20

‘Breakthrough therapy’ status is much sought after, but there is confusion about its definition and impact.

doi: 10.1038/502020a

Features

天文測定学:ヨーロッパの期待の星

Astrometry: Europe's star power p.22

The Gaia spacecraft will soon launch on a mission to chart the heavens in unprecedented detail.

doi: 10.1038/502022a

倫理:タブー視される遺伝学

Ethics: Taboo genetics p.26

Probing the biological basis of certain traits ignites controversy. But some scientists choose to cross the red line anyway.

doi: 10.1038/502026a

News & Views

物性物理学:一緒に居たがる量子

Condensed-matter physics: Quantum togetherness p.40

自由に動き回る1個の励起量子のもう1個の量子による制御が、2つの別々に行われた実験によって実証された。この結果は、情報の処理や転送に関連すると考えられる。

doi: 10.1038/nature12689

幹細胞:完全性まであと一歩

Stem cells: Close encounters with full potential p.41

成熟細胞に幹細胞の能力を付与することは容易ではない。この過程に対する決定的な障壁の1つが、今回明らかにされた。これが除去されれば、ほとんど全ての成熟細胞に幹細胞の性質を効率よく与えることが可能になる。

doi: 10.1038/nature12561

材料科学:長い記憶を持つ合金

Materials science: Alloys with long memories p.42

著しく再現性の高い相転移を数千回にわたって繰り返す合金が作られた。この発見は、変形を受けてもそれ以前の形状を「思い出せる」実用性の高い材料の開発につながりそうだ。

doi: 10.1038/502042a

酵素学:新分野に乗り出すモジュール型生合成

Enzymology: Modular biosynthesis branches out p.44

生物活性を持つ分子に含まれる環状構造は、分子に剛性を生じさせ、これはその分子が標的に選択的にしっかりと結合するのに役立つ。環状構造が形成される機序が明らかになり、生化学では珍しい反応が関わっていることが分かった。

doi: 10.1038/nature12562

生物学実験法:染色体を1つずつ捕捉する方法

Biological techniques: Chromosomes captured one by one p.45

個々の細胞中での染色体の構造と相互作用の解析から得られたデータは、以前に単一細胞画像化と集団平均したゲノム相互作用の研究から得られた結果を統合するものだ。

doi: 10.1038/nature12691

Articles

宇宙:火星のアラビア大陸内の古い火山区にある超巨大火山

Supervolcanoes within an ancient volcanic province in Arabia Terra, Mars p.47

Several irregularly shaped craters located within Arabia Terra, Mars, are interpreted as a new type of highland volcanic construct, similar to supervolcanoes on Earth, fundamentally changing the picture of ancient volcanism and climate evolution on Mars.

doi: 10.1038/nature12482

分子生物学:ヒト転写開始複合体のゲノム内での組織化

Genomic organization of human transcription initiation complexes p.53

The ChIP-exo technique is used to map the organization of transcription initiation complexes across the human genome at near-base-pair resolution; most of the transcription initiation complexes give rise to non-coding, non-polyadenylated RNA, indicating that pervasive non-coding transcription arise from specific promoters and is regulated.

doi: 10.1038/nature12535

遺伝学:単一細胞Hi-C法で明らかになった染色体構造の細胞ごとの変動性

Single-cell Hi-C reveals cell-to-cell variability in chromosome structure p.59

A novel genomic technique, single-cell Hi-C, detects thousands of simultaneous chromatin contacts in a single cell; this is used to show that individual chromosomes maintain domain organization at the megabase scale, but that chromosome structures vary from cell to cell at larger scales.

doi: 10.1038/nature12593

細胞:体細胞の多能性への決定論的な直接再プログラム化

Deterministic direct reprogramming of somatic cells to pluripotency p.65

This study shows that the combination of naive pluripotency growth conditions, Oct4, Sox2, Klf4 and Myc (OSKM) overexpression, and depleting the Mbd3/NuRD co-repressor results in deterministic and synchronized reprogramming to pluripotency.

doi: 10.1038/nature12587

Letters

物理:量子非線形媒質における引き合う光子

Attractive photons in a quantum nonlinear medium p.71

The fundamental properties of light derive from its constituent particles—massless quanta (photons) that do not interact with one another. However, it has long been known that the realization of coherent interactions between individual photons, akin to those associated with conventional massive particles, could enable a wide variety of novel scientific and engineering applications. Here we demonstrate a quantum nonlinear medium inside which individual photons travel as massive particles with strong mutual attraction, such that the propagation of photon pairs is dominated by a two-photon bound state. We achieve this through dispersive coupling of light to strongly interacting atoms in highly excited Rydberg states. We measure the dynamical evolution of the two-photon wavefunction using time-resolved quantum state tomography, and demonstrate a conditional phase shift exceeding one radian, resulting in polarization-entangled photon pairs. Particular applications of this technique include all-optical switching, deterministic photonic quantum logic and the generation of strongly correlated states of light.

doi: 10.1038/nature12512

物理:マグノン束縛状態とそのダイナミクスの微視的観測

Microscopic observation of magnon bound states and their dynamics p.76

The existence of bound states of elementary spin waves (magnons) in one-dimensional quantum magnets was predicted almost 80 years ago. Identifying signatures of magnon bound states has so far remained the subject of intense theoretical research, and their detection has proved challenging for experiments. Ultracold atoms offer an ideal setting in which to find such bound states by tracking the spin dynamics with single-spin and single-site resolution following a local excitation. Here we use in situ correlation measurements to observe two-magnon bound states directly in a one-dimensional Heisenberg spin chain comprising ultracold bosonic atoms in an optical lattice. We observe the quantum dynamics of free and bound magnon states through time-resolved measurements of two spin impurities. The increased effective mass of the compound magnon state results in slower spin dynamics as compared to single-magnon excitations. We also determine the decay time of bound magnons, which is probably limited by scattering on thermal fluctuations in the system. Our results provide a new way of studying fundamental properties of quantum magnets and, more generally, properties of interacting impurities in quantum many-body systems.

doi: 10.1038/nature12541

材料科学:金属ナノ粒子の局在表面プラズモン共鳴の三次元画像化

Three-dimensional imaging of localized surface plasmon resonances of metal nanoparticles p.80

The remarkable optical properties of metal nanoparticles are governed by the excitation of localized surface plasmon resonances (LSPRs). The sensitivity of each LSPR mode, whose spatial distribution and resonant energy depend on the nanoparticle structure, composition and environment, has given rise to many potential photonic, optoelectronic, catalytic, photovoltaic, and gas- and bio-sensing applications. However, the precise interplay between the three-dimensional (3D) nanoparticle structure and the LSPRs is not always fully understood and a spectrally sensitive 3D imaging technique is needed to visualize the excitation on the nanometre scale. Here we show that 3D images related to LSPRs of an individual silver nanocube can be reconstructed through the application of electron energy-loss spectrum imaging, mapping the excitation across a range of orientations, with a novel combination of non-negative matrix factorization, compressed sensing and electron tomography. Our results extend the idea of substrate-mediated hybridization of dipolar and quadrupolar modes predicted by theory, simulations, and electron and optical spectroscopy, and provide experimental evidence of higher-energy mode hybridization. This work represents an advance both in the understanding of the optical response of noble-metal nanoparticles and in the probing, analysis and visualization of LSPRs.

doi: 10.1038/nature12469

材料科学:相変態材料の可逆性向上と特異な微細構造

Enhanced reversibility and unusual microstructure of a phase-transforming material p.85

Materials undergoing reversible solid-to-solid martensitic phase transformations are desirable for applications in medical sensors and actuators, eco-friendly refrigerators and energy conversion devices. The ability to pass back and forth through the phase transformation many times without degradation of properties (termed ‘reversibility’) is critical for these applications. Materials tuned to satisfy a certain geometric compatibility condition have been shown to exhibit high reversibility, measured by low hysteresis and small migration of transformation temperature under cycling. Recently, stronger compatibility conditions called the ‘cofactor conditions’ have been proposed theoretically to achieve even better reversibility. Here we report the enhanced reversibility and unusual microstructure of the first martensitic material, Zn45Au30Cu25, that closely satisfies the cofactor conditions. We observe four striking properties of this material. (1) Despite a transformation strain of 8%, the transformation temperature shifts less than 0.5 °C after more than 16,000 thermal cycles. For comparison, the transformation temperature of the ubiquitous NiTi alloy shifts up to 20 °C in the first 20 cycles. (2) The hysteresis remains approximately 2 °C during this cycling. For comparison, the hysteresis of the NiTi alloy is up to 70 °C (refs 9, 12). (3) The alloy exhibits an unusual riverine microstructure of martensite not seen in other martensites. (4) Unlike that of typical polycrystal martensites, its microstructure changes drastically in consecutive transformation cycles, whereas macroscopic properties such as transformation temperature and latent heat are nearly reproducible. These results promise a concrete strategy for seeking ultra-reliable martensitic materials.

doi: 10.1038/nature12532

地球:南極棚氷の分離フラックスと底面融解速度

Calving fluxes and basal melt rates of Antarctic ice shelves p.89

Iceberg calving has been assumed to be the dominant cause of mass loss for the Antarctic ice sheet, with previous estimates of the calving flux exceeding 2,000 gigatonnes per year. More recently, the importance of melting by the ocean has been demonstrated close to the grounding line and near the calving front. So far, however, no study has reliably quantified the calving flux and the basal mass balance (the balance between accretion and ablation at the ice-shelf base) for the whole of Antarctica. The distribution of fresh water in the Southern Ocean and its partitioning between the liquid and solid phases is therefore poorly constrained. Here we estimate the mass balance components for all ice shelves in Antarctica, using satellite measurements of calving flux and grounding-line flux, modelled ice-shelf snow accumulation rates and a regional scaling that accounts for unsurveyed areas. We obtain a total calving flux of 1,321 ± 144 gigatonnes per year and a total basal mass balance of −1,454 ± 174 gigatonnes per year. This means that about half of the ice-sheet surface mass gain is lost through oceanic erosion before reaching the ice front, and the calving flux is about 34 per cent less than previous estimates derived from iceberg tracking. In addition, the fraction of mass loss due to basal processes varies from about 10 to 90 per cent between ice shelves. We find a significant positive correlation between basal mass loss and surface elevation change for ice shelves experiencing surface lowering and enhanced discharge. We suggest that basal mass loss is a valuable metric for predicting future ice-shelf vulnerability to oceanic forcing.

doi: 10.1038/nature12567

進化:単一遺伝子座に生じる生活史的なトレードオフが、性選択を受ける形質の遺伝的変動を維持する

Life history trade-offs at a single locus maintain sexually selected genetic variation p.93

Sexual selection, through intra-male competition or female choice, is assumed to be a source of strong and sustained directional selection in the wild. In the presence of such strong directional selection, alleles enhancing a particular trait are predicted to become fixed within a population, leading to a decrease in the underlying genetic variation. However, there is often considerable genetic variation underlying sexually selected traits in wild populations, and consequently, this phenomenon has become a long-discussed issue in the field of evolutionary biology. In wild Soay sheep, large horns confer an advantage in strong intra-sexual competition, yet males show an inherited polymorphism for horn type and have substantial genetic variation in their horn size. Here we show that most genetic variation in this trait is maintained by a trade-off between natural and sexual selection at a single gene, relaxin-like receptor 2 (RXFP2). We found that an allele conferring larger horns, Ho+, is associated with higher reproductive success, whereas a smaller horn allele, HoP, confers increased survival, resulting in a net effect of overdominance (that is, heterozygote advantage) for fitness at RXFP2. The nature of this trade-off is simple relative to commonly proposed explanations for the maintenance of sexually selected traits, such as genic capture (‘good genes’) and sexually antagonistic selection. Our results demonstrate that by identifying the genetic architecture of trait variation, we can determine the principal mechanisms maintaining genetic variation in traits under strong selection and explain apparently counter-evolutionary observations.

doi: 10.1038/nature12489

微生物学:微生物叢が遊離させた宿主の糖は腸内病原菌の抗生物質投与後の増殖を促進する

Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens p.96

The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella enterica serovar Typhimurium (S. typhimurium) and Clostridium difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of Bacteroides thetaiotaomicron, a model gut symbiont, reduces free sialic acid levels resulting in C. difficile downregulating its sialic acid catabolic pathway and exhibiting impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens.

doi: 10.1038/nature12503

免疫:高病原性SIVに感染した場合の免疫によるクリアランス

Immune clearance of highly pathogenic SIV infection p.100

Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIVmac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma- or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69–172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.

doi: 10.1038/nature12519

免疫:podoplaninは血小板CLEC-2と相互作用することにより、高内皮細静脈の完全性を維持する

Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2 p.105

Circulating lymphocytes continuously enter lymph nodes for immune surveillance through specialized blood vessels named high endothelial venules, a process that increases markedly during immune responses. How high endothelial venules (HEVs) permit lymphocyte transmigration while maintaining vascular integrity is unknown. Here we report a role for the transmembrane O-glycoprotein podoplanin (PDPN, also known as gp38 and T1α) in maintaining HEV barrier function. Mice with postnatal deletion of Pdpn lost HEV integrity and exhibited spontaneous bleeding in mucosal lymph nodes, and bleeding in the draining peripheral lymph nodes after immunization. Blocking lymphocyte homing rescued bleeding, indicating that PDPN is required to protect the barrier function of HEVs during lymphocyte trafficking. Further analyses demonstrated that PDPN expressed on fibroblastic reticular cells, which surround HEVs, functions as an activating ligand for platelet C-type lectin-like receptor 2 (CLEC-2, also known as CLEC1B). Mice lacking fibroblastic reticular cell PDPN or platelet CLEC-2 exhibited significantly reduced levels of VE-cadherin (also known as CDH5), which is essential for overall vascular integrity, on HEVs. Infusion of wild-type platelets restored HEV integrity in Clec-2-deficient mice. Activation of CLEC-2 induced release of sphingosine-1-phosphate from platelets, which promoted expression of VE-cadherin on HEVs ex vivo. Furthermore, draining peripheral lymph nodes of immunized mice lacking sphingosine-1-phosphate had impaired HEV integrity similar to Pdpn- and Clec-2-deficient mice. These data demonstrate that local sphingosine-1-phosphate release after PDPN–CLEC-2-mediated platelet activation is critical for HEV integrity during immune responses.

doi: 10.1038/nature12501

細胞生物学:サイクリンAは動原体微小管を調節して正確な染色体分離を促す

Cyclin A regulates kinetochore microtubules to promote faithful chromosome segregation p.110

The most conspicuous event in the cell cycle is the alignment of chromosomes in metaphase. Chromosome alignment fosters faithful segregation through the formation of bi-oriented attachments of kinetochores to spindle microtubules. Notably, numerous kinetochore–microtubule (k–MT) attachment errors are present in early mitosis (prometaphase), and the persistence of those errors is the leading cause of chromosome mis-segregation in aneuploid human tumour cells that continually mis-segregate whole chromosomes and display chromosomal instability. How robust error correction is achieved in prometaphase to ensure error-free mitosis remains unknown. Here we show that k–MT attachments in prometaphase cells are considerably less stable than in metaphase cells. The switch to more stable k–MT attachments in metaphase requires the proteasome-dependent destruction of cyclin A in prometaphase. Persistent cyclin A expression prevents k–MT stabilization even in cells with aligned chromosomes. By contrast, k–MTs are prematurely stabilized in cyclin-A-deficient cells. Consequently, cells lacking cyclin A display higher rates of chromosome mis-segregation. Thus, the stability of k–MT attachments increases decisively in a coordinated fashion among all chromosomes as cells transit from prometaphase to metaphase. Cyclin A creates a cellular environment that promotes microtubule detachment from kinetochores in prometaphase to ensure efficient error correction and faithful chromosome segregation.

doi: 10.1038/nature12507

生物物理:グルタミン酸輸送体ホモログの輸送動態

Transport dynamics in a glutamate transporter homologue p.114

Glutamate transporters are integral membrane proteins that catalyse neurotransmitter uptake from the synaptic cleft into the cytoplasm of glial cells and neurons. Their mechanism of action involves transitions between extracellular (outward)-facing and intracellular (inward)-facing conformations, whereby substrate binding sites become accessible to either side of the membrane. This process has been proposed to entail transmembrane movements of three discrete transport domains within a trimeric scaffold. Using single-molecule fluorescence resonance energy transfer (smFRET) imaging, we have directly observed large-scale transport domain movements in a bacterial homologue of glutamate transporters. We find that individual transport domains alternate between periods of quiescence and periods of rapid transitions, reminiscent of bursting patterns first recorded in single ion channels using patch-clamp methods. We propose that the switch to the dynamic mode in glutamate transporters is due to separation of the transport domain from the trimeric scaffold, which precedes domain movements across the bilayer. This spontaneous dislodging of the substrate-loaded transport domain is approximately 100-fold slower than subsequent transmembrane movements and may be rate determining in the transport cycle.

doi: 10.1038/nature12265

生物物理:三量体であるナトリウム依存性アスパラギン酸輸送体の単一分子中で起こる同期しないサブユニット運動

Unsynchronised subunit motion in single trimeric sodium-coupled aspartate transporters p.119

Excitatory amino acid transporters (EAATs) are secondary transport proteins that mediate the uptake of glutamate and other amino acids. EAATs fulfil an important role in neuronal signal transmission by clearing the excitatory neurotransmitters from the synaptic cleft after depolarization of the postsynaptic neuron. An intensively studied model system for understanding the transport mechanism of EAATs is the archaeal aspartate transporter GltPh. Each subunit in the homotrimeric GltPh supports the coupled translocation of one aspartate molecule and three Na+ ions as well as an uncoupled flux of Cl ions. Recent crystal structures of GltPh revealed three possible conformations for the subunits, but it is unclear whether the motions of individual subunits are coordinated to support transport. Here, we report the direct observation of conformational dynamics in individual GltPh trimers embedded in the membrane by applying single-molecule fluorescence resonance energy transfer (FRET). By analysing the transporters in a lipid bilayer instead of commonly used detergent micelles, we achieve conditions that approximate the physiologically relevant ones. From the kinetics of FRET level transitions we conclude that the three GltPh subunits undergo conformational changes stochastically and independently of each other.

doi: 10.1038/nature12538

生化学:専用のポリケチドシンターゼモジュールが触媒するビニログ的分枝鎖形成

Vinylogous chain branching catalysed by a dedicated polyketide synthase module p.124

Bacteria use modular polyketide synthases (PKSs) to assemble complex polyketides, many of which are leads for the development of clinical drugs, in particular anti-infectives and anti-tumoral agents. Because these multifarious compounds are notoriously difficult to synthesize, they are usually produced by microbial fermentation. During the past two decades, an impressive body of knowledge on modular PKSs has been gathered that not only provides detailed insight into the biosynthetic pathways but also allows the rational engineering of enzymatic processing lines to yield structural analogues. Notably, a hallmark of all PKS modules studied so far is the head-to-tail fusion of acyl and malonyl building blocks, which leads to linear backbones. Yet, structural diversity is limited by this uniform assembly mode. Here we demonstrate a new type of PKS module from the endofungal bacterium Burkholderia rhizoxinica that catalyses a Michael-type acetyl addition to generate a branch in the carbon chain. In vitro reconstitution of the entire PKS module, X-ray structures of a ketosynthase-branching didomain and mutagenesis experiments revealed a crucial role of the ketosynthase domain in branching the carbon chain. We present a trapped intermediary state in which acyl carrier protein and ketosynthase are covalently linked by the branched polyketide and suggest a new mechanism for chain alkylation, which is functionally distinct from terpenoid-like β-branching. For the rice seedling blight toxin rhizoxin, one of the strongest known anti-mitotic agents, the non-canonical polyketide modification is indispensable for phytotoxic and anti-tumoral activities. We propose that the formation of related pharmacophoric groups follows the same general scheme and infer a unifying vinylogous branching reaction for PKS modules with a ketosynthase-branching–acyl-carrier-protein architecture. This study unveils the structure and function of a new PKS module that broadens the biosynthetic scope of polyketide biosynthesis and sets the stage for rationally creating structural diversity.

doi: 10.1038/nature12588

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