Abstract:
:PdxB (erythronate 4-phosphate dehydrogenase) is expected to be required for synthesis of the essential cofactor pyridoxal 5'-phosphate (PLP) in Escherichia coli Surprisingly, incubation of the ∆pdxB strain in medium containing glucose as a sole carbon source for 10 d resulted in visible turbidity, suggesting that PLP is being produced by some alternative pathway. Continued evolution of parallel lineages for 110 to 150 generations produced several strains that grow robustly in glucose. We identified a 4-step bypass pathway patched together from promiscuous enzymes that restores PLP synthesis in strain JK1. None of the mutations in JK1 occurs in a gene encoding an enzyme in the new pathway. Two mutations indirectly enhance the ability of SerA (3-phosphoglycerate dehydrogenase) to perform a new function in the bypass pathway. Another disrupts a gene encoding a PLP phosphatase, thus preserving PLP levels. These results demonstrate that a functional pathway can be patched together from promiscuous enzymes in the proteome, even without mutations in the genes encoding those enzymes.
journal_name
Proc Natl Acad Sci U S Aauthors
Kim J,Flood JJ,Kristofich MR,Gidfar C,Morgenthaler AB,Fuhrer T,Sauer U,Snyder D,Cooper VS,Ebmeier CC,Old WM,Copley SDdoi
10.1073/pnas.1915569116subject
Has Abstractpub_date
2019-11-26 00:00:00pages
24164-24173issue
48eissn
0027-8424issn
1091-6490pii
1915569116journal_volume
116pub_type
杂志文章abstract::Acetyl-CoA synthase from Clostridium thermoaceticum (ACS(Ct)) is an alpha(2)beta(2) tetramer containing two novel Ni-X-Fe(4)S(4) active sites (the A and C clusters) and a standard Fe(4)S(4) cluster (the B cluster). The acsA and acsB genes encoding the enzyme were cloned into Escherichia coli strain JM109 and overexpre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.220404397
更新日期:2000-11-07 00:00:00
abstract::Inferring causal effects from observational and interventional data is a highly desirable but ambitious goal. Many of the computational and statistical methods are plagued by fundamental identifiability issues, instability, and unreliable performance, especially for large-scale systems with many measured variables. We...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1510493113
更新日期:2016-07-05 00:00:00
abstract::1-Aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14), extracted from tomato pericarp tissue, was purified 6500-fold by conventional and high-performance liquid chromatography. Two-dimensional gel electrophoresis of this preparation indicated that ACC synthase activity was associated with a protein band at 50...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.20.7755
更新日期:1986-10-01 00:00:00
abstract::Food choices are shifting globally in ways that are negatively affecting both human health and the environment. Here we consider how consuming an additional serving per day of each of 15 foods is associated with 5 health outcomes in adults and 5 aspects of agriculturally driven environmental degradation. We find that ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1906908116
更新日期:2019-11-12 00:00:00
abstract::The origins and consequences of a regulatory T cell (Treg) disorder in systemic lupus erythematosus (SLE) are poorly understood. In the (NZBxNZW) F(1) mouse model of lupus, we found that CD4(+)Foxp3(+) Treg failed to maintain a competitive pool size in the peripheral lymphoid organs resulting in a progressive homeosta...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0903158107
更新日期:2010-01-05 00:00:00
abstract::We have investigated the interaction of human cytomegalovirus (CMV) with cultured primary granulocyte-macrophage progenitors, a suspected natural site of viral latency, and have established conditions for latent infection and reactivation in this cell population. Progenitor cells from human fetal liver or bone marrow ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.25.11879
更新日期:1994-12-06 00:00:00
abstract::It is believed that neural representations of recent experiences become reactivated during sleep, and that this process serves to stabilize associated memories in long-term memory. Here, we initiated this reactivation process for specific memories during slow-wave sleep. Participants studied 50 object-location associa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1201072109
更新日期:2012-06-26 00:00:00
abstract::Although still poorly understood, the chemistry that occurs on the surfaces of interstellar dust particles profoundly affects the growth of molecules in the interstellar medium. The most important surface reaction is the conversion of atomic to molecular hydrogen, which is a precursor for all subsequent molecular deve...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601556103
更新日期:2006-08-15 00:00:00
abstract::Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (+/-)-7beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.18.5513
更新日期:1982-09-01 00:00:00
abstract::Cellular imbalance in the levels of antioxidants and reactive oxygen species resulting in apoptosis is directly associated with a number of parasitic infections, aging, and several genetic and multifactorial diseases. The baculovirus AcNPV-encoded antiapoptotic p35 gene prevents apoptosis induced by a variety of apopt...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.9.4838
更新日期:1999-04-27 00:00:00
abstract::For most intracellular structures with larger than molecular dimensions, little is known about the connection between underlying molecular activities and higher order organization such as size and shape. Here, we show that both the size and shape of the amphibian oocyte nucleolus ultimately arise because nucleoli beha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1017150108
更新日期:2011-03-15 00:00:00
abstract::Assembly of protein complexes is a key mechanism for achieving spatial and temporal coordination in processes involving many enzymes. Growth of rod-shaped bacteria is a well-studied example requiring such coordination; expansion of the cell wall is thought to involve coordination of the activity of synthetic enzymes w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1313826111
更新日期:2014-03-25 00:00:00
abstract::To assess the effect of transforming growth factor beta 1 on the skin in vivo, we have targeted its expression to the epidermis of transgenic mice. To ensure that active TGF-beta 1 was expressed, we used a porcine TGF-beta 1 cDNA with mutations of Cys-223-->Ser and Cys-225-->Ser, which allow constitutive activation. M...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.11.5237
更新日期:1993-06-01 00:00:00
abstract::Recent evidence suggests that the Myc and Mad1 proteins are implicated in the regulation of the gene encoding the human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. We have analyzed the in vivo interaction between endogenous c-Myc and Mad1 proteins and the hTERT promoter in HL60 cells...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.071043198
更新日期:2001-03-27 00:00:00
abstract::Ectopic expression of transcription factors can reprogram somatic cells to a pluripotent state. However, most of the studies used skin fibroblasts as the starting population for reprogramming, which usually take weeks for expansion from a single biopsy. We show here that induced pluripotent stem (iPS) cells can be gen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0908450106
更新日期:2009-09-15 00:00:00
abstract::Single cortical neurons in the mammalian brain receive signals arising from multiple sensory input channels. Dendritic integration of these afferent signals is critical in determining the amplitude and time course of the neurons' output signals. As of yet, little is known about the spatial and temporal organization of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1112355108
更新日期:2011-09-13 00:00:00
abstract::Heat shock factors (HSFs) are the master regulators of transcription under protein-damaging conditions, acting in an environment where the overall transcription is silenced. We determined the genomewide transcriptional program that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our results rev...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1305275110
更新日期:2013-09-03 00:00:00
abstract::The effect of RNA secondary structure on rho-independent and rho-dependent termination of transcription of T3 DNA by Escherichia coli RNA polymerase has been studied by incorporating, into nascent transcripts, base analogs that lead to altered base-pairing properties. A guanine --> hypoxanthine substitution, with atte...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.4.1613
更新日期:1979-04-01 00:00:00
abstract::Monocytes originate from precursors made in the bone and remain in the circulation for nearly 24 h. Much effort has been done to identify the molecules regulating transendothelial migration of monocytes during inflammatory conditions. In contrast, considerably less is known about the process of constitutive monocyte e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0700732104
更新日期:2007-03-27 00:00:00
abstract::Microbial fatty acid derivatives are emerging as promising alternatives to fossil fuel derived transportation fuels. Among bacterial fatty acid synthases (FAS), the Escherichia coli FAS is perhaps the most well studied, but little is known about its steady-state kinetic behavior. Here we describe the reconstitution of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1110852108
更新日期:2011-11-15 00:00:00
abstract::The complete amino acid and DNA sequences of the human 40-kDa keratin are reported. The DNA sequence encodes a protein of 44,098 Da, which is unique in that it lacks the terminal non-alpha-helical tail segment found in all other keratins. When the human 40-kDa keratin amino acid sequence is compared to the correspondi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.4.1114
更新日期:1988-02-01 00:00:00
abstract::Experimental circular dichroic (CD) spectra of three proteins have been combined with estimates of the content of peptide-chain structural modes obtained from x-ray diffraction studies of the same proteins. Solution of the simultaneous equations at a series of wavelengths permits the construction of a CD spectrum for ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.5.969
更新日期:1971-05-01 00:00:00
abstract::The study of gene family members has been aided by the isolation of related genes on the basis of DNA homology. We have adapted the polymerase chain reaction to screen animal genomes very rapidly and reliably for likely gene family members. Using conserved amino acid sequences to design degenerate oligonucleotide prim...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.12.4372
更新日期:1989-06-01 00:00:00
abstract::Human and murine MHC nonclassical class Ib-restricted invariant T (iT) cell subsets, such as invariant natural killer T cells (iNKT) and mucosal-associated invariant T cells, have specialized functions early in immune responses, especially in modulating subsequent adaptive immune responses. Here, we characterize a pro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1309840110
更新日期:2013-08-27 00:00:00
abstract::We report a combined thermodynamic and structural characterization of a DNA tetraplex. Using spectroscopic and calorimetric techniques, we demonstrate that d(TG3T) and d(TG3T2G3T), in the presence of K+, form stable tetramolecular complexes. From differential scanning calorimetry measurements, we obtain the following ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.18.8832
更新日期:1992-09-15 00:00:00
abstract::New experiments using scanning probe microcopies and advanced optical methods allow us to study molecules as individuals, not just as populations. The findings of these studies not only include the confirmation of results expected from studies of bulk matter, but also give substantially new information concerning the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.20.11075
更新日期:1999-09-28 00:00:00
abstract::The antimicrobial peptide hepcidin appears to play a central role in the regulation of iron homeostasis. In intact animals, iron overload or the injection of lipopolysaccharide (LPS) stimulates transcription of HAMP, the gene that encodes hepcidin. In isolated hepatocytes, IL-6, an inflammatory cytokine the production...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0403108101
更新日期:2004-06-22 00:00:00
abstract::We compute parameters characterizing many-body quantum chaos for a critical Fermi surface without quasiparticle excitations. We examine a theory of [Formula: see text] species of fermions at nonzero density coupled to a [Formula: see text] gauge field in two spatial dimensions and determine the Lyapunov rate and the b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1618185114
更新日期:2017-02-21 00:00:00
abstract::Ecosystem restoration aims to restore biodiversity and valuable functions that have been degraded or lost. The Coral Triangle is a hotspot for marine biodiversity held in its coral reefs, seagrass meadows, and mangrove forests, all of which are in global decline. These coastal ecosystems support valuable fisheries and...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1707962114
更新日期:2017-11-07 00:00:00
abstract::Genetic analysis of Parkinson disease (PD) has identified several genes whose mutation causes inherited parkinsonism, as well as risk loci for sporadic PD. PTEN-induced kinase 1 (PINK1) and parkin, linked to autosomal recessive PD, act in a common genetic pathway regulating the autophagic degradation of mitochondria, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1321207111
更新日期:2014-06-10 00:00:00