Abstract：
:Polysialic acid (polySia) is a posttranslational modification found on only a handful of proteins in the central nervous and immune systems. The addition of polySia to therapeutic proteins improves pharmacokinetics and reduces immunogenicity. To date, polysialylation of therapeutic proteins has only been achieved in vitro by chemical or chemoenzymatic strategies. In this work, we develop a biosynthetic pathway for site-specific polysialylation of recombinant proteins in the cytoplasm of Escherichia coli. The pathway takes advantage of a bacterial cytoplasmic polypeptide-glycosyltransferase to establish a site-specific primer on the target protein. The glucose primer is extended by glycosyltransferases derived from lipooligosaccharide, lipopolysaccharide and capsular polysaccharide biosynthesis from different bacterial species to synthesize long chain polySia. We demonstrate the new biosynthetic route by modifying green fluorescent proteins and a therapeutic DARPin (designed ankyrin repeat protein).
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Keys TG,Wetter M,Hang I,Rutschmann C,Russo S,Mally M,Steffen M,Zuppiger M,Müller F,Schneider J,Faridmoayer A,Lin CW,Aebi Mdoi
10.1016/j.ymben.2017.10.012subject
Has Abstractpub_date
2017-11-01 00:00:00pages
293-301eissn
1096-7176issn
1096-7184pii
S1096-7176(17)30235-5journal_volume
44pub_type
杂志文章abstract：:Valine, which is one of the branched-chain amino acids (BCAAs) essential for humans, is widely used in animal feed, dietary supplements and pharmaceuticals. At the commercial level, valine is usually produced by bacterial fermentation from glucose. However, valine biosynthesis can also proceed in the yeast Saccharomyc...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.02.011
更新日期：2018-03-01 00:00:00
abstract：:An engineered reversal of the β-oxidation cycle (r-BOX) and the fatty acid biosynthesis (FAB) pathway are promising biological platforms for advanced fuel and chemical production in part due to their iterative nature supporting the synthesis of various chain length products. While diverging in their carbon-carbon elon...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.11.003
更新日期：2018-01-01 00:00:00
abstract：:Malonyl-CoA is the basic building block for synthesizing a range of important compounds including fatty acids, phenylpropanoids, flavonoids and non-ribosomal polyketides. Centering around malonyl-CoA, we summarized here the various metabolic engineering strategies employed recently to regulate and control malonyl-CoA ...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2017.10.011
更新日期：2017-11-01 00:00:00
abstract：:Isobutanol is a valuable chemical and is considered a new generation biofuel. Construction of isobutanol synthesis pathways in bacteria is a hot topic in isobutanol production. Here, we show that an isobutanol synthesis pathway exists naturally in Klebsiella pneumoniae; however, this pathway is dormant in the wild-typ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.07.003
更新日期：2017-09-01 00:00:00
abstract：:Lipogenic organisms provide an ideal platform for biodiesel and oleochemical production. Through our previous rational metabolic engineering efforts, lipogenesis titers in Yarrowia lipolytica were significantly enhanced. However, the resulting strain still suffered from decreased biomass generation rates. Here, we emp...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.02.003
更新日期：2015-05-01 00:00:00
abstract：:Succinic acid is a platform chemical of recognized industrial value and accordingly faces a continuous challenge to enable manufacturing from most attractive raw materials. It is mainly produced from glucose, using microbial fermentation. Here, we explore and optimize succinate production from sucrose, a globally appl...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.10.003
更新日期：2017-11-01 00:00:00
abstract：:Fatty acids are the most abundant form of reduced carbon chains available from nature and have diverse uses ranging from food to industrial feedstocks. Plants represent a significant renewable source of fatty acids because many species accumulate them in the form of triacylglycerol as major storage components in seeds...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1006/mben.2001.0204
更新日期：2002-01-01 00:00:00
abstract：:Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of bio...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.11.005
更新日期：2018-01-01 00:00:00
abstract：:Caffeic acid has been widely recognized as a versatile pharmacophore for synthesis of new chemical entities, among which caffeic acid derived phenethyl esters and amides are the most extensively-investigated bioactive compounds with potential therapeutical applications. However, the natural biosynthetic routes for caf...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.09.011
更新日期：2017-11-01 00:00:00
abstract：:One of the main strategies to improve the production of relevant metabolites has been the manipulation of single or multiple key genes in the metabolic pathways. This kind of strategy requires several rounds of experiments to identify enzymes that impact either yield or productivity. The use of mathematical tools to f...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2009.04.002
更新日期：2009-07-01 00:00:00
abstract：:β-Oxidation is the ubiquitous metabolic strategy to break down fatty acids. In the course of this four-step process, two carbon atoms are liberated per cycle from the fatty acid chain in the form of acetyl-CoA. However, typical β-oxidative strategies are not restricted to monocarboxylic (fatty) acid degradation only, ...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2017.05.004
更新日期：2017-07-01 00:00:00
abstract：:Parthenolide, the main bioactive compound of the medicinal plant feverfew (Tanacetum parthenium), is a promising anti-cancer drug. However, the biosynthetic pathway of parthenolide has not been elucidated yet. Here we report on the isolation and characterization of all the genes from feverfew that are required for the...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.03.005
更新日期：2014-05-01 00:00:00
abstract：:Cyclic guanosine monophosphate (cGMP) is a universal second messenger that is synthesized from guanosine triphosphate (GTP) by guanylyl cyclases (GCs) and hydrolyzed into guanosine monophosphate (GMP) by phosphodiesterases (PDEs). Small-molecule drugs that induce high cGMP levels in specialized tissues by boosting GC ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.03.016
更新日期：2015-05-01 00:00:00
abstract：:The potential to produce succinate aerobically in Escherichia coli would offer great advantages over anaerobic fermentation in terms of faster biomass generation, carbon throughput, and product formation. Genetic manipulations were performed on two aerobic succinate production systems to increase their succinate yield...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2004.10.003
更新日期：2005-03-01 00:00:00
abstract：:High titer 1-butanol production in Escherichia coli has previously been achieved by overexpression of a modified clostridial 1-butanol production pathway and subsequent deletion of native fermentation pathways. This strategy couples growth with production as 1-butanol pathway offers the only available terminal electro...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.04.003
更新日期：2017-05-01 00:00:00
abstract：:Two types of non-homologous beta-carotene ketolases (CrtW and CrtO) were previously described. We report improvement of a CrtO-type of beta-carotene ketolase for canthaxanthin production in a methylotrophic bacterium, Methylomonas sp. 16a, which could use the C1 substrate (methane or methanol) as sole carbon and energ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.05.004
更新日期：2007-07-01 00:00:00
abstract：:An efficient production process is important for industrial microorganisms. The cellular efficiency of solventogenic clostridia, a group of anaerobes capable of producing a wealth of bulk chemicals and biofuels, must be improved for competitive commercialization. Here, using Clostridium acetobutylicum, a species of so...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.02.006
更新日期：2016-05-01 00:00:00
abstract：:Discovery of the cold-inducible RNA-binding protein (CIRP) in mouse fibroblasts suggests that growth suppression at hypothermic conditions is due to an active response by the cell rather than due to passive thermal effects. To determine the effect of down-regulated CIRP expression on cell growth and erythropoietin (EP...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.11.003
更新日期：2007-03-01 00:00:00
abstract：BACKGROUND:6-Methylsalicylic acid synthase (MSAS), a fungal polyketide synthase from Penicillium patulum, is perhaps the simplest polyketide synthase that embodies several hallmarks of this family of multifunctional enzymes--a large multidomain protein, a high degree of specificity toward acetyl-CoA and malonyl-CoA sub...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.1999.0113
更新日期：1999-04-01 00:00:00
abstract：:Aromatic amino acids are precursors of numerous plant secondary metabolites with diverse biological functions. Many of these secondary metabolites are already being used as active pharmaceutical or nutraceutical ingredients, and there are numerous exploratory studies of other compounds with promising applications. p-C...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.08.003
更新日期：2015-09-01 00:00:00
abstract：:Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. Currently, industrial production of simvastatin acid (SVA) is a multistep process starting from the natural product lovastatin. For this reason, there is significant interest in direct production of simvasta...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.09.005
更新日期：2019-01-01 00:00:00
abstract：:Genetic manipulation in cyanobacteria enables the direct production of valuable chemicals from carbon dioxide. However, there are still very few reports of the production of highly effective photosynthetic chemicals. Several synthetic metabolic pathways (e.g., isopropanol, acetone, isoprene, and fatty acids) have been...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2019.07.012
更新日期：2020-01-01 00:00:00
abstract：:The de novo synthesis of triglyceride (TG) fatty acids (FA) and glycerol can be measured with stable isotope tracers. However, these methods typically do not inform the contribution of a given substrate to specific pathways on these synthetic processes. We integrated deuterated water (2H2O) measurement of de novo lipo...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2019.08.018
更新日期：2019-12-01 00:00:00
abstract：:The chemical monomer p-hydroxystyrene (pHS) is used for producing a number of important industrial polymers from petroleum-based feedstocks. In an alternative approach, the microbial production of pHS can be envisioned by linking together a number of different metabolic pathways, of which those based on using glucose ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2007.01.002
更新日期：2007-05-01 00:00:00
abstract：:A large number of CHO glycosylation mutants were isolated by Ricinus communis agglutinin-I (RCA-I). Complementation tests revealed that all these mutant lines possessed a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. Sequencing analyses on the GnT I cDNAs isolated from 16 mutant lines led to the identi...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2010.03.002
更新日期：2010-07-01 00:00:00
abstract：:Selective estrogen receptor (ER) modulators are highly successful breast cancer therapies, but they are not effective in patients with ER negative and selective estrogen receptor modulator (SERM)-resistant tumors. Understanding the mechanisms of estrogen-stimulated proliferation may provide a route to design estrogen-...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.06.005
更新日期：2006-11-01 00:00:00
abstract：:Biosynthesis of Nylon 12 monomer using dodecanoic acid (DDA) or its esters as the renewable feedstock typically involves ω-hydroxylation, oxidation and ω-amination. The dependence of hydroxylation and oxidation-catalyzing enzymes on redox cofactors, and the requirement of L-alanine as the co-substrate and pyridoxal 5'...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.09.006
更新日期：2020-11-01 00:00:00
abstract：:Plants are versatile chemists producing a tremendous variety of specialized compounds. Here, we describe the engineering of entirely novel metabolic pathways in planta enabling generation of halogenated indigo precursors as non-natural plant products. Indican (indolyl-β-D-glucopyranoside) is a secondary metabolite cha...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.02.003
更新日期：2018-03-01 00:00:00
abstract：:The promise of plants to serve as the green factories of the future is ever increasing. Plants have been used traditionally for construction, energy, food and feed. Bioactive compounds primarily derived from specialized plant metabolism continue to serve as important scaffold molecules for pharmaceutical drug producti...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2014.11.005
更新日期：2015-01-01 00:00:00
abstract：:As synthetic pathways built from exogenous enzymes become more complicated, the probability of encountering undesired interactions with host organisms increases, thereby lowering product titer. An emerging strategy to combat this problem is to spatially organize pathway enzymes into multi-protein complexes, where high...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2011.09.003
更新日期：2012-05-01 00:00:00
