Abstract：
:FK506, a widely used immunosuppressant, is produced by industrial fermentation processes using various Streptomyces species. Independently of the strain, structurally related compound FK520 is co-produced, resulting in complex and costly isolation procedures. In this paper, we report a chemobiosynthetic approach for exclusive biosynthesis of FK506. This approach is based on the Streptomyces tsukubaensis strain with inactivated allR gene, a homologue of crotonyl-CoA carboxylase/reductase, encoded in the FK506 biosynthetic cluster. This strain produces neither FK506 nor FK520; however, if allylmalonyl-S-N-acetylcysteamine precursor is added to cultivation broth, the production of FK506 is reestablished without FK506-related by-products. Using a combination of metabolic engineering and chemobiosynthetic approach, we achieved exclusive production of FK506, representing a significant step towards development of an advanced industrial bioprocess.
journal_name
Metab Engjournal_title
Metabolic engineeringauthors
Kosec G,Goranovič D,Mrak P,Fujs S,Kuščer E,Horvat J,Kopitar G,Petković Hdoi
10.1016/j.ymben.2011.11.003subject
Has Abstractpub_date
2012-01-01 00:00:00pages
39-46issue
1eissn
1096-7176issn
1096-7184pii
S1096-7176(11)00119-4journal_volume
14pub_type
杂志文章abstract：:Synthesis of polyketides at high titer and yield is important for producing pharmaceuticals and biorenewable chemical precursors. In this work, we engineered cofactor and transport pathways in Saccharomyces cerevisiae to increase acetyl-CoA, an important polyketide building block. The highly regulated yeast pyruvate d...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.02.009
更新日期：2016-07-01 00:00:00
abstract：:This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and fi...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.01.001
更新日期：2012-03-01 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：:Acid-tolerant Saccharomyces cerevisiae was engineered to produce lactic acid by expressing heterologous lactate dehydrogenase (LDH) genes, while attenuating several key pathway genes, including glycerol-3-phosphate dehydrogenase1 (GPD1) and cytochrome-c oxidoreductase2 (CYB2). In order to increase the yield of lactic ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.09.006
更新日期：2016-05-01 00:00:00
abstract：:The construction of large DNA molecules that encode pathways, biological machinery, and entire genomes has been limited to the reproduction of natural sequences. However, now that robust methods for assembling hundreds of DNA fragments into constructs > 20 kb are readily available, optimization of large genetic elemen...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2012.02.005
更新日期：2012-05-01 00:00:00
abstract：:Predicting resource allocation between cell processes is the primary step towards decoding the evolutionary constraints governing bacterial growth under various conditions. Quantitative prediction at genome-scale remains a computational challenge as current methods are limited by the tractability of the problem or by ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.10.003
更新日期：2015-11-01 00:00:00
abstract：:An innovative "biodrug" concept based on oral administration of living recombinant microorganisms as a vehicle to deliver active compounds directly into the digestive tract has recently been developed. To validate this concept, we studied a recombinant Saccharomyces cerevisiae strain in order to investigate its viabil...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2009.01.001
更新日期：2009-05-01 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：:Pigmented metabolites have great potential for use in biosensors that target low-resource areas, since sensor output can be interpreted without any equipment. However, full repression of pigment production when undesired is challenging, as even small amounts of enzyme can catalyze the production of large, visible amou...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2017.07.004
更新日期：2017-09-01 00:00:00
abstract：:Crocins and picrocrocin are glycosylated apocarotenoids responsible, respectively, for the color and the unique taste of the saffron spice, known as red gold due to its high price. Several studies have also shown the health-promoting properties of these compounds. However, their high costs hamper the wide use of these...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.06.009
更新日期：2020-09-01 00:00:00
abstract：:A mathematical model to describe carbon catabolite repression in Escherichia coli is developed and in part validated. The model is aggregated from two functional units describing glucose and lactose transport and degradation. Both units are members of the crp modulon and are under control of a global signal transducti...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1006/mben.2001.0199
更新日期：2001-10-01 00:00:00
abstract：:3-Ketosteroid-△(1)-dehydrogenase (KstD) is a key enzyme involved in the microbial catabolism of sterols. Here, three homologues of KstD were characterized from Mycobacterium neoaurum ATCC 25795, showing distinct substrate preferences and transcriptional responses to steroids. Single deletion of any MN-kstD failed to r...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.05.005
更新日期：2014-07-01 00:00:00
abstract：:A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information e...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/s1096-7176(03)00023-5
更新日期：2003-04-01 00:00:00
abstract：:A novel strategy to finely control a large metabolic flux by using a "metabolic transistor" approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its ...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.01.002
更新日期：2015-03-01 00:00:00
abstract：:The modularity and versatility of an engineered functional reversal of the β-oxidation cycle make it a promising platform for the synthesis of longer-chain (C≥4) products. While the pathway has recently been exploited for the production of n-alcohols and carboxylic acids, fully capitalizing on its potential for the sy...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.02.011
更新日期：2014-05-01 00:00:00
abstract：:Xylose, which is a major constituent of lignocellulosic biomass, was utilized for the production of poly(lactate-co-3-hydroxybutyrate) [P(LA-co-3HB)], having transparent and flexible properties. The recombinant Escherichia coli JW0885 (pflA(-)) expressing LA-polymerizing enzyme (LPE) and monomer supplying enzymes grow...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.11.007
更新日期：2013-01-01 00:00:00
abstract：:Cyanobacteria hold promise as a cell factory for producing biofuels and bio-derived chemicals, but genome engineering of cyanobacteria such as Synechococcus elongatus PCC 7942 poses challenges because of their oligoploidy nature and long-term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA-gui...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2016.09.006
更新日期：2016-11-01 00:00:00
abstract：:Metabolic models used in 13C metabolic flux analysis generally include a limited number of reactions primarily from central metabolism. They typically omit degradation pathways, complete cofactor balances, and atom transition contributions for reactions outside central metabolism. This study addresses the impact on pr...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.08.006
更新日期：2015-11-01 00:00:00
abstract：:One of the key drivers for successful metabolic engineering in microbes is the efficacy by which genomes can be edited. As such there are many methods to choose from when aiming to modify genomes, especially those of model organisms like yeast and bacteria. In recent years, clustered regularly interspaced palindromic ...
journal_title：Metabolic engineering
pub_type： 杂志文章,评审
doi：10.1016/j.ymben.2015.12.003
更新日期：2016-03-01 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：:Intense synthesis of proteins and chemicals in engineered microbes impose metabolic burden, frequently leading to reduced growth and heterogeneous cell population. Thus, the correct balance between growth and production is important. Such balance can be engineered through dynamic control of pathways, but few broadly a...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2020.03.012
更新日期：2020-09-01 00:00:00
abstract：:Cyanobacteria can be exploited as photosynthetic platforms for heterologous generation of terpene hydrocarbons with industrial applications. Transformation of Synechocystis and heterologous expression of the β-phellandrene synthase (PHLS) gene alone is necessary and sufficient to confer to Synechocystis the ability to...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2015.09.010
更新日期：2015-11-01 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：:Geobacter species are among the most effective microorganisms known for the bioremediation of radioactive and toxic metals in contaminated subsurface environments and for converting organic compounds to electricity in microbial fuel cells. However, faster rates of electron transfer could aid in optimizing these proces...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2008.06.005
更新日期：2008-09-01 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：:Previous metabolic engineering strategies for improving glycerol production by Saccharomyces cerevisiae were constrained to a maximum theoretical glycerol yield of 1 mol.(molglucose)(-1) due to the introduction of rigid carbon, ATP or redox stoichiometries. In the present study, we sought to circumvent these constrain...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2006.06.004
更新日期：2006-11-01 00:00:00
abstract：:Successful redirection of endogenous resources into heterologous pathways is a central tenet in the creation of efficient microbial cell factories. This redirection, however, may come at a price of poor biomass accumulation, reduced cofactor regeneration and low recombinant enzyme expression. In this study, we propose...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.08.006
更新日期：2012-11-01 00:00:00
abstract：:The glycolipid synthase MG517 from Mycoplasma genitalium catalyzes the glucosyl transfer from UDPGlc to diacylglycerol producing glycoglycerolipids (GGL) (Andrés et al., 2011). The enzyme was functional in E. coli accumulating GGL in the plasma membrane. A metabolic engineering strategy for GGL production was evaluate...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2012.06.001
更新日期：2012-09-01 00:00:00
abstract：:The biological nitrogen fixation carried out by some Bacteria and Archaea is one of the most attractive alternatives to synthetic nitrogen fertilizers. In this study we compared the effect of controlling the maximum activation state of the Azotobacter vinelandii glutamine synthase by a point mutation at the active sit...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2014.03.002
更新日期：2014-05-01 00:00:00
abstract：:Natural products are a rich source of potential drugs for many applications. Discovery of natural products through the activation of cryptic gene clusters encoding their biosynthetic pathways, engineering of those biosynthetic pathways and optimization of production yields often rely on the expression of these gene cl...
journal_title：Metabolic engineering
pub_type： 杂志文章
doi：10.1016/j.ymben.2018.09.004
更新日期：2018-09-01 00:00:00
