Abstract:
:Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recode, construct and characterize the biosynthetic pathway of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We use a green fluorescent protein (GFP) mapping strategy to identify the low expression of Bik1 (polyketide synthase) as a major bottleneck step in the pathway, and a promoter exchange strategy is used to increase expression of Bik1 and bikaverin titer. Then, we use an enzyme-fusion strategy to directly couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to an improved titer of bikaverin at 202.75 mg/L with flask fermentation (273-fold higher than the initial titer). This study demonstrates that the biosynthesis of complex fungal polyketides can be established and efficiently engineered in S. cerevisiae, highlighting the potential for natural product synthesis and large-scale fermentation in yeast.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Zhao M,Zhao Y,Yao M,Iqbal H,Hu Q,Liu H,Qiao B,Li C,Skovbjerg CAS,Nielsen JC,Nielsen J,Frandsen RJN,Yuan Y,Boeke JDdoi
10.1038/s41467-020-19984-3subject
Has Abstractpub_date
2020-12-03 00:00:00pages
6197issue
1issn
2041-1723pii
10.1038/s41467-020-19984-3journal_volume
11pub_type
杂志文章abstract::Analyzing scattered wave to recognize object is of fundamental significance in wave physics. Recently-emerged deep learning technique achieved great success in interpreting wave field such as in ultrasound non-destructive testing and disease diagnosis, but conventionally need time-consuming computer postprocessing or ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19693-x
更新日期:2020-12-09 00:00:00
abstract::Unusual features of the vibrational density of states D(ω) of glasses allow one to rationalize their peculiar low-temperature properties. Simulational studies of D(ω) have been restricted to studying poorly annealed glasses that may not be relevant to experiments. Here we report on D(ω) of zero-temperature glasses wit...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07978-1
更新日期:2019-01-03 00:00:00
abstract::A subtle balance between competing interactions in iron-based superconductors (FeSCs) can be tipped by additional interfacial interactions in a heterostructure, often inducing exotic phases with unprecedented properties. Particularly when the proximity-coupled layer is magnetically active, rich phase diagrams are expe...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02327-0
更新日期:2017-12-18 00:00:00
abstract::Mismatch repair (MMR)-deficient cancers are characterized by microsatellite instability (MSI) and hypermutation. However, it remains unclear how MSI and hypermutation arise and contribute to cancer development. Here, we show that MSI and hypermutation are triggered by replication stress in an MMR-deficient background,...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11760-2
更新日期:2019-09-02 00:00:00
abstract::The need for sustainable catalysts for an efficient hydrogen evolution reaction is of significant interest for modern society. Inspired by comparable structural properties of [FeNi]-hydrogenase, here we present the natural ore pentlandite (Fe4.5Ni4.5S8) as a direct 'rock' electrode material for hydrogen evolution unde...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12269
更新日期:2016-07-27 00:00:00
abstract::Forests are of major importance to human society, contributing several crucial ecosystem services. Biodiversity is suggested to positively influence multiple services but evidence from natural systems at scales relevant to management is scarce. Here, across a scale of 400,000 km(2), we report that tree species richnes...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2328
更新日期:2013-01-01 00:00:00
abstract::In nature, individual cells contain multiple isolated compartments in which cascade enzymatic reactions occur to form essential biological products with high efficiency. Here, we report a cell-inspired design of functional hydrogel particles with multiple compartments, in which different enzymes are spatially immobili...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00757-4
更新日期:2017-09-22 00:00:00
abstract::Merons are nontrivial topological spin textures highly relevant for many phenomena in solid state physics. Despite their importance, direct observation of such vortex quasiparticles is scarce and has been limited to a few complex materials. Here, we show the emergence of merons and antimerons in recently discovered tw...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-20497-2
更新日期:2021-01-08 00:00:00
abstract::How spatial and temporal information are integrated to determine the direction of cell migration remains poorly understood. Here, by precise microfluidics emulation of dynamic chemoattractant waves, we demonstrate that, in Dictyostelium, directional movement as well as activation of small guanosine triphosphatase Ras ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6367
更新日期:2014-11-06 00:00:00
abstract::Over the last century the North Anatolian Fault Zone in Turkey has produced a remarkable sequence of large earthquakes. These events have now left an earthquake gap south of Istanbul and beneath the Marmara Sea, a gap that has not been filled for 250 years. Here we investigate the nature of the eastern end of this gap...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2999
更新日期:2013-01-01 00:00:00
abstract::Subduction zone magmas are more oxidised on eruption than those at mid-ocean ridges. This is attributed either to oxidising components, derived from subducted lithosphere (slab) and added to the mantle wedge, or to oxidation processes occurring during magma ascent via differentiation. Here we provide direct evidence f...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05804-2
更新日期:2018-08-29 00:00:00
abstract::High-index dielectric nanoparticles supporting a distinct series of Mie resonances have enabled a new class of optical antennas with unprecedented functionalities. The great wealth of multipolar responses has not only brought in new physical insight but also spurred practical applications. However, how to make such a ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-08057-1
更新日期:2019-01-23 00:00:00
abstract::Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth an...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-20527-z
更新日期:2021-01-12 00:00:00
abstract::The search for a method that utilizes biological information to predict humans' place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation seq...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4513
更新日期:2014-04-29 00:00:00
abstract::Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochon...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10226-9
更新日期:2019-06-12 00:00:00
abstract::It has previously been shown that the relative reliability of model-based and model-free reinforcement-learning (RL) systems plays a role in the allocation of behavioral control between them. However, the role of task complexity in the arbitration between these two strategies remains largely unknown. Here, using a com...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13632-1
更新日期:2019-12-16 00:00:00
abstract::The role of the histamine H3 receptor (H3R) in cerebral ischaemia/reperfusion (I/R) injury remains unknown. Here we show that H3R expression is upregulated after I/R in two mouse models. H3R antagonists and H3R knockout attenuate I/R injury, which is reversed by an H3R-selective agonist. Interestingly, H1R and H2R ant...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4334
更新日期:2014-02-25 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature communications
pub_type: 已发布勘误
doi:10.1038/s41467-019-13458-x
更新日期:2019-11-26 00:00:00
abstract::Calcareous microplankton shells form the dominant components of ancient and modern pelagic sea-floor carbonates and are widely used in palaeoenvironmental reconstructions. The efficacy of these applications, however, is dependent upon minimal geochemical alteration during diagenesis, but these modifying processes are ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3052
更新日期:2013-01-01 00:00:00
abstract::Infrared light detection and sensing is deeply embedded in modern technology and human society and its development has always been benefitting from the discovery of various photoelectric materials. The rise of two-dimensional materials, thanks to their distinct electronic structures, extreme dimensional confinement an...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05874-2
更新日期:2018-08-17 00:00:00
abstract::Nanopatterning by molecular self-assembly has been a topic of intense research in pursuit of 'bottom-up' methods of generating structures for use in nanotechnology. The systems most widely studied have been two- and three-dimensional morphologies of block copolymers. However, T- and X-shaped polyphilic liquid crystals...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2096
更新日期:2012-01-01 00:00:00
abstract::Recent studies show that the D'' layer, just above the Earth's core-mantle boundary, is composed of MgSiO3 post-perovskite and has significant lateral inhomogeneity. Here we consider the D'' diversity as related to the single-crystal elasticity of the post-perovskite phase. We measure the single-crystal elasticity of ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4453
更新日期:2014-03-27 00:00:00
abstract::Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that the motor protein myosin-Va works with dynamic actin tracks to drive long-range organe...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17212-6
更新日期:2020-07-13 00:00:00
abstract::Complex tissue-specific and cell-specific signaling by the estrogen receptor (ER) frequently leads to the development of resistance to endocrine therapy for breast cancer. Pure ER antagonists, which completely lack tissue-specific agonist activity, hold promise for preventing and treating endocrine resistance, however...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04413-3
更新日期:2018-06-18 00:00:00
abstract::Adult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. It is unclear if stem cell niche signals coordinate fate decisions within the progenitor pool. Here we use quantitative analysis of Wnt, Hh, and Notch signalling reporters and the cell fate mark...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01322-9
更新日期:2017-11-01 00:00:00
abstract::The original version of this article contained an error in the spelling of Juan Pedro Martinez-Barbera, which was incorrectly given as Juan Pedro Martinez Barbera. This error has now been corrected in both the PDF and HTML versions of the Article. ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-018-05718-z
更新日期:2018-08-02 00:00:00
abstract::HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man9-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03565-6
更新日期:2018-03-16 00:00:00
abstract::Thanks to the nature of strong programmability, field-programmable gate arrays (FPGAs) have been playing a significant role in signal processing and control. With the explosive growth in digital data, big data analytics becomes an important emerging field, in which FPGAs are a major player. However, the computational ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-14249-0
更新日期:2020-01-21 00:00:00
abstract::Genetic noise together with genome duplication and volume changes during cell cycle are significant contributors to cell-to-cell heterogeneity. How can cells buffer the effects of these unavoidable epigenetic and genetic variations on phenotypes that are sensitive to such variations? Here we show that a simple network...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12959
更新日期:2016-10-03 00:00:00
abstract::Non-linear interactions in coherent gases are not only at the origin of bright and dark solitons and superfluids; they also give rise to phenomena such as multistability, which hold great promise for the development of advanced photonic and spintronic devices. In particular, spinor multistability in strongly coupled s...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3008
更新日期:2013-01-01 00:00:00