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PubMed1994

Signal peptide hydrophobicity is finely tailored for function.

In order to titrate the dependence of individual steps in protein transport on signal peptide hydrophobicity, we have examined a series of mutants which involve replacement of the hydrophobic core segment of the Escherichia coli alkaline phosphatase signal peptide. The core regions vary in composition from 10:0 to 0:10 in the ratio of alanine to leucine residues. Thus, a nonfunctional polyalanine-containing signal peptide is titrated with the more hydrophobic residue, leucine. Analysis of this series identified a midpoint for rapid precursor processing between alanine to leucine ratios of 6:4 and 5:5 [Doud et al. (1993): Biochemistry 32:1251-1256]. Examination of precursors that are processed more slowly indicates a lower limit of signal peptide hydrophobicity that permits membrane association and translocation. Analysis of precursors that are processed rapidly defines an intermediate range of hydrophobicity that is optimum; above this level precursors become insensitive to transport inhibitors such as sodium azide and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in parallel with substantial inhibition of beta-lactamase processing. Our data indicate that there is a surprisingly narrow range of signal peptide hydrophobicity which both supports transport of the protein to which it is attached and which does not have such a high affinity for the transport pathway that it disrupts the appropriate balance of other secreted proteins.

Alanine↗
PubMed1985

Mast-cell precursors in the skin of mouse embryos and their deficiency in embryos of Sl/Sld genotype.

Concentration of mast-cell precursors in the skin and liver of mouse embryos was evaluated by the limiting dilution analysis. The concentration of mast-cell precursors in the liver of (WB X C57BL/6)F1 (hereafter WBB6F1)-+/+ embryos reached the maximum level at Day 15 of the pregnancy, whereas the concentration in the skin at Day 17. The concentration of 17-day skin was about 10 times as high as that of 15-day liver. Appearance of morphologically identifiable mast cells in the skin followed the increase in concentration of the skin precursors. Concentrations of mast-cell precursors in the skin and liver of mutant embryos of Sl/Sld genotype were also measured to clarify the mechanism of mast-cell depletion in this mutant. Although the concentration of mast-cell precursors in the liver of WBB6F1-Sl/Sld embryos was comparable to that of the WBB6F1-+/+ embryos, the concentration in the skin of the Sl/Sld embryos was about 1% that of the +/+ embryos. Moreover, the concentration of morphologically identifiable mast cells in the skin of the Sl/Sld embryos was about 0.1% that of the +/+ embryos. Thus, mast-cell production in Sl/Sld embryos seemed to be suppressed at two stages; (1) during deficient invasion of liver-derived precursors into the skin, or the decreased proliferation of these cells, or both of these causes, (2) during differentiation of the precursors into mast cells.

Animals↗
PubMed1999

Development of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of fabricius.

Immunoglobulin gene rearrangement in avian B cell precursors generates surface Ig receptors of limited diversity. It has been proposed that specificities encoded by these receptors play a critical role in B lineage development by recognizing endogenous ligands within the bursa of Fabricius. To address this issue directly we have introduced a truncated surface IgM, lacking variable region domains, into developing B precursors by retroviral gene transfer in vivo. Cells expressing this truncated receptor lack endogenous surface IgM, and the low level of endogenous Ig rearrangements that have occurred within this population of cells has not been selected for having a productive reading frame. Such cells proliferate rapidly within bursal epithelial buds of normal morphology. In addition, despite reduced levels of endogenous light chain rearrangement, those light chain rearrangements that have occurred have undergone variable region diversification by gene conversion. Therefore, although surface expression of an Ig receptor is required for bursal colonization and the induction of gene conversion, the specificity encoded by the prediversified receptor is irrelevant and, consequently, there is no obligate ligand for V(D)J-encoded determinants of prediversified avian cell surface IgM receptor.

Amino Acid Sequence↗
PubMed1988

Human cytomegalovirus-specific cytotoxic T cells: their precursor frequency and stage specificity.

Human virus-specific cytotoxic T (Tc) cells may be important in maintaining the virus/host equilibrium during persistent herpes virus infections such as that with human cytomegalovirus (HCMV). We have previously shown that HCMV-specific Tc cells are present in peripheral blood in normal asymptomatic seropositive individuals (L. K. Borysiewicz et al., Eur. J. Immunol. 1983. 13: 804). In this study we have used limiting dilution analysis to estimate the precursor frequency of these Tc cells and to further delineate their specificity for viral proteins expressed at different stages of the virus replicative cycle. HCMV-specific Tc precursor cells were present in peripheral blood lymphocytes (PBL) at a frequency of 1/5000 to 20,000 E+ PBL. This frequency was higher than that observed for varicella-zoster virus (VZV)-specific Tc cells (1/30,000 to greater than 500,000) in asymptomatic individuals and was similar to the VZV Tc precursor cell frequencies observed following clinical reactivation (1/30,000). When the stage specificity of clonally derived HCMV-specific Tc cells was analyzed, using target cells treated with phosphonoformate to allow expression of only the nonstructural viral proteins, the majority (60%) of Tc cells lysed these cells. A number of Tc cells lysed only cells which expressed the structural or late HCMV proteins. These results suggest a high precursor frequency of HCMV-specific Tc cells in PBL, and that there are subpopulations of such Tc cells specific for HCMV antigens expressed at different stages of the virus replicative cycle. However, the relative frequencies of these subpopulations suggest that the immunodominant HCMV antigens with respect to the Tc response are expressed at immediate early and/or early times.

Cells, Cultured↗
PubMed2005

Diverse spreading behavior of binary polymer nanodroplets.

Molecular dynamics simulations are used to study the spreading of binary polymer nanodroplets in a cylindrical geometry. The polymers, described by the bead-spring model, spread on a flat surface with a surface-coupled Langevin thermostat to mimic the effects of a corrugated surface. Each droplet consists of chains of length 10 or 100 monomers with approximately 350,000 monomers total. The qualitative features of the spreading dynamics are presented for differences in chain length, surface interaction strength, and composition. When the components of the droplet differ only in the surface interaction strength, the more strongly wetting component forms a monolayer film on the surface even when both materials are above or below the wetting transition. In the case where the only difference is the polymer chain length, the monolayer film beneath the droplet is composed of an equal amount of short chain and long chain monomers even when one component (the shorter chain length) is above the wetting transition and the other is not. The fraction of short and long chains in the precursor foot depends on whether both the short and the long chains are in the wetting regime. Diluting the concentration of the strongly wetting component in a mixture with a weakly wetting component decreases the rate of diffusion of the wetting material from the bulk to the surface and limits the spreading rate of the precursor foot, but the bulk spreading rate actually increases when both components are present. This may be due to the strongly wetting material pushing out the weakly wetting material as it moves toward the precursor foot.

Journal Article↗
PubMed2005

Gene network inference from incomplete expression data: transcriptional control of hematopoietic commitment.

MOTIVATION: The topology and function of gene regulation networks are commonly inferred from time series of gene expression levels in cell populations. This strategy is usually invalid if the gene expression in different cells of the population is not synchronous. A promising, though technically more demanding alternative is therefore to measure the gene expression levels in single cells individually. The inference of a gene regulation network requires knowledge of the gene expression levels at successive time points, at least before and after a network transition. However, owing to experimental limitations a complete determination of the precursor state is not possible. RESULTS: We investigate a strategy for the inference of gene regulatory networks from incomplete expression data based on dynamic Bayesian networks. This permits prediction of the number of experiments necessary for network inference depending on parameters including noise in the data, prior knowledge and limited attainability of initial states. Our strategy combines a gradual 'Partial Learning' approach based solely on true experimental observations for the network topology with expectation maximization for the network parameters. We illustrate our strategy by extensive computer simulations in a high-dimensional parameter space in a simulated single-cell-based example of hematopoietic stem cell commitment and in random networks of different sizes. We find that the feasibility of network inferences increases significantly with the experimental ability to force the system into different initial network states, with prior knowledge and with noise reduction. AVAILABILITY: Source code is available under: www.izbi.uni-leipzig.de/services/NetwPartLearn.html SUPPLEMENTARY INFORMATION: Supplementary Data are available at Bioinformatics online.

Algorithms↗
PubMed1982

Modulation of in vitro BFU-E growth by normal Ia-positive T cells is restricted by HLA-DR.

The in vitro growth of immature erythroid precursors, assayed as burst forming units (BFU-E), can be enhanced by co-culturing with normal T cells. The growth enhancing effect of normal T cells, however, was shown to be the outcome of at least two functionally distinct subpopulations, one that enhances burst formation and one that limits it. It appears that the T cell population limiting growth enhancement of the erythroid precursors expresses 'Ia-like' antigen (Ia+) because treatment of T cells with anti-Ia antibody and complement significantly increased the ability of the remaining T cells to stimulate antologous BFU-E growth. As BFU-E also seem to express Ia, the inhibiting effect of certain T cells on BFU-E growth may involve the Ia molecule. We show here that the inhibitory effect of Ia+ T cells on BFU-E growth is genetically restricted to cell combinations which are phenotypically identical for at least one HLA-DR (Ia-like) antigen.

Adult↗
PubMed1981

Recognition of polymorphic H-2 domains by T lymphocytes. I. Functional role of different H-2 domains for the generation of alloreactive cytotoxic T lymphocytes and determination of precursor frequencies.

In the present communication, the repertoire of alloreactive cytotoxic T lymphocytes (CTL) clones was quantitatively investigated by limiting dilution analysis and by target inhibition with a panel of monoclonal antibodies (mAb). These mAb have previously been shown to define two distinct alloantigenic domains, A and B, on the H-2Kk molecule. The Poisson distribution analysis of H-2Kk-specific CTL clones generated in a limiting dilution system revealed three CTL populations with different precursor frequencies. The high frequent population is suppressed by an unknown suppressive mechanism that allows less frequent CTL populations to become visible. Target inhibition studies with a panel of Kk-specific mAb showed that these CTL populations differ not only in their precursor frequency but also in their specificity for different H-2 epitopes on the Kk molecule. Thus clones of the high frequency population are almost exclusively specific for determinants within domain A. In contrast, the low frequency population displays predominant specificity for determinants of domain B, while the population with medium frequency is blocked equally well by mAb against either domains A or B. Each mAb blocked only a fraction of clones indicating that each CTL subpopulation may consist of a large number of clonotypes with specificity for different H-2 epitopes. The data suggest that CTL recognize basically the same polymorphic domains on the H-2Kk molecule defined by antibodies, and they show that regulatory mechanisms determine the expressed repertoire in CTL populations.

Animals↗
PubMed1991

Processing enzyme specificity is a consequence of pro-hormone precursor protein conformation.

Peptide-hormones are synthesized as higher molecular weight, precursor proteins which must initially undergo limited endoproteolysis to yield the bioactive peptide(s). The ability of two different endoproteinases, gonadotropin-associated peptide (GAP)-releasing enzyme and atrial granule serine proteinase (which are likely to be the physiologically relevant processing enzymes of bovine hypothalamic pro-gonadotropin-releasing hormone/gonadotropin-associated peptide and bovine pro-atrial natriuretic factor precursor proteins, respectively), to act at their own recognition sequences within their relevant pro-hormone proteins has now been contrasted with their ability to act at the recognition sequence for the alternate enzyme or to act at their own recognition sequence when it is placed within the protein framework of the alternate precursor protein. The results show that each enzyme acts with specificity at its own recognition sequence even when it is placed within the framework of the alternate pro-hormone. However, the enzymes fail to act (or act in a non-specific manner) at the alternate recognition sequence even if it is placed within the peptide framework of its own pro-hormone protein. Thus, despite the fact that both recognition sequences are similar in sequence and residue composition and that both contain a doublet of basic amino acids, it appears that sequence and the local conformation assumed by the processing site within the pro-hormone protein are essential for each endoproteinase to act with fidelity. As part of our continuing work, we now also report several newly determined physicochemical properties of hypothalamic GAP-releasing enzyme, the processing enzyme of pro-gonadotropin-releasing hormone/GAP protein.

Amino Acid Sequence↗
PubMed1989

Interpretation of cancer prevention trials.

Principles and methods to guide interpretation require a different emphasis for cancer trials. Assumptions used to design a trial must be validated and modified during the trial to avoid limitations. To maximize information from such trials, recruitment strategies for commonly free-living subjects, measurements of safety and compliance, and ascertainment with pathologic review of endpoints must be obtained. Consideration of multiple endpoints may provide a better interpretation of cancer prevention for skin, colon, and transient occurrences illustrated by cervical dysplasia or biochemical precursors. A careful definition of the limitations of preventive trials is required. These include the actual size of the intervention groups, completeness and duration of follow-up, and comparison between trial participants and a defined source population. To obtain a valid interpretation with adequate precision of intervention effectiveness, time to endpoints should be evaluated using statistical multivariate methods such as Cox proportional hazard or relative risk models. These permit adjustment for important confounding and risk modifiers such as compliance, dietary intake, and drift in control group. The magnitude of the intervention efficacy and the generalizability of results of the trial will be negatively impacted if the intervention has a delayed (latent) effect. Such delay in intervention effect requires added considerations with possible extension of trial duration. Use of confidence limits for intervention effectiveness provides added insight and improved interpretation of prevention trials. The final component of a cancer prevention trial, as with any study, is to interpret and report its results. Providing a valid interpretation with adequate precision to hypotheses of a cancer prevention trial requires added emphasis on the accuracy of the assumptions made to design the trial and the duration of the trial. Design assumptions regarding compliance to the prescribed interventions, time until the experimental intervention achieves full effect, and the frequency of endpoints directly impact on the number of endpoints observed. Terminating a cancer prevention trial before adequate information is obtained, thus severely flawing its interpretation, requires ongoing awareness. Interpretation of a cancer prevention trial should include several added steps: first, investigators to critically review the actual manner in which the trial was conducted; second, carry out an appropriate analysis of the data; and third, review the results and note exceptions or limitations in the data. The results of the trial should be contrasted with previous studies. Implications of the results to future trials should be considered. Finally, these interpretations should be documented in a written report and made available to the scientific community.

Clinical Trials as Topic↗
PubMed1986

Mechanism of synergy between T cell signals and C8-substituted guanine nucleosides in humoral immunity: B lymphotropic cytokines induce responsiveness to 8-mercaptoguanosine.

B lymphocytes require a source of T cell-like help to produce antibody to T cell-dependent antigens. T cell-derived lymphokines and C8-substituted guanine ribonucleosides (such as 8-mercaptoguanosine; 8MGuo) are effective sources of such T cell-like help. Addition of T cell-derived lymphokines to antigen-activated B cells together with 8MGuo results in synergistic B cell differentiation, amplifying the sum of the individual responses twofold to four-fold. Lymphokine activity is required at initiation of culture for optimal synergy with 8MGuo, whereas the nucleoside can be added up to 48 hr after the lymphokines with full synergy. 8MGuo provides a perceived T cell-like differentiation signal to B cells from immunodeficient xid mice, thereby distinguishing a subset of Lyb-5- nucleoside-responsive B cells from those activated by soluble anti-mu followed by B cell stimulatory factor-1, interleukin 1, and B cell differentiation factors, which are Lyb-5+. Moreover, at least a subset of the B cells recruited by the synergistic interaction of lymphokines and nucleoside is distinct from that responsive to 8MGuo + antigen, insofar as Sephadex G-10 nonadherent xid B cells fail to respond to either 8MGuo or lymphokines alone, but do respond to the combination. A distinct subpopulation can also be demonstrated among normal B cells by limiting dilution analysis in which the precursor frequency of antigen-reactive B cells in the presence of lymphokines or nucleoside alone increases substantially when both agents are present together. In concert with the kinetic data, these observations suggest that synergy derives at least in part from the ability of lymphokines to induce one or more elements the absence of which limits the capacity of a distinct B cell subpopulation to respond to 8MGuo.

Animals↗
PubMed1996

Regulation of prostaglandin synthesis in Madin Darby canine kidney cells: role of prostaglandin G/H synthase and secreted phospholipase A2.

The renal epithelial cell line MDCK (Madin Darby canine kidney) was used as a model system to investigate the contribution of the secreted phospholipase A2 type II(sPLA2) and cyclooxygenases to prostaglandin E2 (PGE2) synthesis. Activation of protein kinase C by the phorbol ester TPA led to an enhanced PGE2 synthesis within 1 hour, which continued for more than 20 hours. Treatment of the cells with TPA increased the activities of sPLA2 and cyclooxygenase. Activation of cyclooxygenase was reflected by an increase in cyclooxygenase-2 mRNA. Coincubation of the cells with TPA and a specific sPLA2 inhibitor (BM 16.2224) almost completely inhibited sPLA2 activity in the cell culture supernatants. TPA-induced PGE2 synthesis was reduced by the inhibitor to about 50%. The inhibitor had no effect on cyclooxygenase activity or expression, indicating an involvement of sPLA2 in PGE2 synthesis. These experiments show that in resting cells, even in the presence of exogenous arachidonic acid, PGE2 synthesis was limited by the low abundance of cyclooxygenase. Enhanced expression and activity of cyclooxygenase, however, was not sufficient for increased prostaglandin synthesis. Availability of the precursor arachidonic acid seemed to be rate limiting in prostaglandin synthesis in stimulated MDCK cells.

Animals↗
PubMed2005

Novel heparan sulphate analogues: inhibition of beta-secretase cleavage of amyloid precursor protein.

The role of HS (heparan sulphate) in the pathology of AD (Alzheimer's disease) is multifaceted. HS and other glycosaminoglycans have been widely reported to be associated with neuritic plaques. HS has also been shown to promote the aggregation of Abeta (amyloid beta-peptide), the proteinaceous component of neuritic plaques. Recently, we described a novel and contrasting role for HS in the pathology of AD: HS can inhibit the formation of Abeta, by directly interacting with the protease BACE1 (beta-site amyloid precursor protein cleaving enzyme 1; beta-secretase 1), that cleaves the amyloid precursor protein and is the rate limiting step in the generation of Abeta. Here, we review the current roles of HS and the potential for HS-derivatives in the treatment of AD.

Alzheimer Disease↗
PubMedDate not supplied

High-level gene expression for recombinant penicillin acylase production using the araB promoter system in Escherichia coli.

The pac gene encoding penicillin acylase (PAC) was overexpressed under the regulation of the araB promoter (ParaB, also known as PBAD) in Escherichia coli (E. coli). The current ParaB expression system exhibited minimum leaking pac expression in the absence of arabinose as well as fast and high-level pac expression upon induction with arabinose in a wide concentration range. The production of PAC was limited by the accumulation of PAC precursors (i.e., proPAC in both soluble and insoluble forms) and various negative cellular responses, such as growth arrest and cell lysis. The culture performance could be improved by degP coexpression and the individual contribution of DegP protease and chaperone activities to the enhancement on the production of PAC was characterized. The study highlights the importance of identifying the step(s) limiting high-level gene expression and subsequent design and construction of the host/vector system for enhancing recombinant protein production in E. coli.

Escherichia coli↗
PubMed1992

Fibroblast growth factor stimulates photoreceptor differentiation in vitro.

Dissociated newborn rat retinal cells were maintained in monolayer culture for periods of up to 11 d. When grown in the absence of exogenous growth factors, 1-2% of the total neuronal population expressed opsin (the photopigment that is specific for maturing photoreceptors). Addition of a single dose of 10 ng/ml basic fibroblast growth factor (bFGF) to the culture medium induced an average increase of sixfold in the numbers of neurons expressing opsin. This supplementation had little effect on the total number of differentiated neurons or of glial cells when measured at the same time points. Furthermore, another specific class of retinal neurons, the amacrine cells, showed no changes following exposure to this growth factor. Two other growth factors known to exert neurotrophic effects, epidermal and nerve growth factor, were without effect. The effect of bFGF was dose dependent, with highly significant differences being observed with as little as 100 pg/ml, and with 700 pg/ml eliciting half-maximal stimulation; maximal effects were observed at 10 ng/ml. Induction of opsin expression by low concentrations of bFGF was blocked completely by an antiserum directed specifically against bFGF, but not by preimmune serum immunoglobulins. This increase in the number of photoreceptors expressing opsin following exposure to bFGF could have been due to either increased cell survival, increased proliferation of progenitor cells, or increased differentiation of immature photoreceptors. There was no increase in overall cell survival under the experimental conditions used, and double labeling immunocytochemistry combined with autoradiographic analysis of 3H-thymidine uptake showed that proliferation of neuronal precursors was not enhanced by the addition of bFGF. In contrast to these observations, cultures established from older (postnatal day 3) retina revealed large numbers of opsin-expressing photoreceptors in all culture plates, with or without added growth factors. This reduction in the stimulatory effects of bFGF with increasing postnatal age is consistent with the period of sensitivity being limited to the cycling of neuronal precursors. It is possible that a bFGF-like molecule is secreted by neighboring cells such as the retinal pigmented epithelium, to participate in retinal development and differentiation. To our understanding, this molecule is the first protein identified to influence specifically the differentiation of photoreceptor cells.

Aging↗
PubMed1988

Characterization of prothymocytes with cloning capacity in human bone marrow.

The identity of human bone marrow (BM)-derived T cell precursors with colony forming capacity has led to controversy because of contamination with mature clonogenic T cells. We achieved 2 Log elimination of mature T cells from BM using a cocktail of monoclonal antibodies: CD2, CD3, CD4, CD6, and CD8 followed by two successive baby rabbit C' treatment. T cell depleted BM can generate colonies of CD2+, CD3+, Ti+, mostly CD4+, in the presence of PHA, rIL2, and a prothymocyte differentiating activity derived from phytohemagglutinin (PHA) induced mononuclear cells. These precursors could be enriched three- to sixfold by percoll gradient centrifugation and then significantly bypass the number of contaminant mature T cells as shown by limiting dilution analysis. Colony generation by marrow precursors was inhibited by the addition of autologous T cells. This inhibition was mostly caused by the T8+ subset. CFU-TL growth was dramatically inhibited by eliminating CD7+ cells suggesting their positivity for this surface marker. These precursors needed major histocompatibility complex (MHC) II-positive cells for optimal growth but lack DR themselves.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1976

Mechanisms of adhesion among cells from neural tissues of the chick embryo.

In order to analyze the molecular mechanisms of cell adhesion during development, proteins on the surface of chick embryonic neural cells were compared with proteins released after placing these cells in culture. One of the components released into culture, F1 (molecular weight, Mr 140,000), was derived by proteolytic cleavage of a cell surface precursor with a molecular weight of at least 240,000. Another protein, F2, recovered from culture as a dimer (Mr 1110,000), appeared to be a product of limited proteolytic cleavage of F1. Cells in retinal tissue possessed a surface protein of Mr 150,000 that also appeared to be derived by limited proteolytic cleavage of the cell surface precursor. Antibodies to F2 interacted with determinants on the cell surface protein of Mr 150,000, and specifically prevented homologous and heterologous binding among dissociated retinal and brain cells. In contrast, antibodies to F1 failed to prevent cell-cell adhesion and did not crossreact with F2. These data suggest that the cell surface protein of Mr 150,000 generated by limited proteolysis is involved in adhesion of both retinal and brain cells. Cell-cell binding of both retinal and brain cells varied as a function of developmental age and brain cells acquired their binding properties at an earlier time than retinal cells. Similar results were obtained in experiments on the binding of retinal and brain cells of different ages to nylon fibres coated with antibodies to F2. The results of the molecular and cellular experiments are incorporated in a model for cell adhesion invoking both proteolytic activation and modulation of cell surface ligands.

Age Factors↗
PubMed1999

Redirection of carbon flux to lysine in a recombinant of Corynebacterium lactofermentum ATCC 21799 by limited supply of pantothenate.

To increase carbon flux to lysine, minimized production of amino acids that are biosynthetically related to lysine, for example, isoleucine and valine, is required. By limiting the supply of pantothenate, the precursor of coenzyme A, the carbon flux was redirected from isoleucine and valine to lysine in the recombinant of Corynebacterium lactofermentum ATCC 21799 containing the plasmid pGC77. The pGC77 contains hom(dr), thrB, and ilvA encoding feedback-deregulated homoserine dehydrogenase, homoserine kinase, and threonine dehydratase, respectively. At 250 microM of isopropyl-beta-d-thiogalactopyranoside, the recombinant (pGC77) produced lysine, valine, and isoleucine. Limiting the supply of pantothenate from 300 microg/l to 30 microg/l resulted in an increase in lysine (from 4.5 to 6.4 g/l) and decreases in valine (from 3.1 to 1.6 g/l) and isoleucine (from 0.9 to 0.3 g/l) production. The concentration of pyruvate was higher and that of acetate lower in the pantothenate-limited culture than in the control, suggesting that the limited supply of pantothenate delayed the conversion of pyruvate to acetyl-CoA. Increased availability of pyruvate by limiting the supply of pantothenate might favor the integration of pyruvate into the lysine branch. The results of this study are useful for the production of lysine with decreased concentrations of byproducts.

Journal Article↗