Rapid engineering of polyketide overproduction by gene transfer to industrially optimized strains.


:Development of natural products for therapeutic use is often hindered by limited availability of material from producing organisms. The speed at which current technologies enable the cloning, sequencing, and manipulation of secondary metabolite genes for production of novel compounds has made it impractical to optimize each new organism by conventional strain improvement procedures. We have exploited the overproduction properties of two industrial organisms- Saccharopolyspora erythraea and Streptomyces fradiae, previously improved for erythromycin and tylosin production, respectively-to enhance titers of polyketides produced by genetically modified polyketide synthases (PKSs). An efficient method for delivering large PKS expression vectors into S. erythraea was achieved by insertion of a chromosomal attachment site ( attB) for phiC31-based integrating vectors. For both strains, it was discovered that only the native PKS-associated promoter was capable of sustaining high polyketide titers in that strain. Expression of PKS genes cloned from wild-type organisms in the overproduction strains resulted in high polyketide titers whereas expression of the PKS gene from the S. erythraea overproducer in heterologous hosts resulted in only normal titers. This demonstrated that the overproduction characteristics are primarily due to mutations in non-PKS genes and should therefore operate on other PKSs. Expression of genetically engineered erythromycin PKS genes resulted in production of erythromycin analogs in greatly superior quantity than obtained from previously used hosts. Further development of these hosts could bypass tedious mutagenesis and screening approaches to strain improvement and expedite development of compounds from this valuable class of natural products.


Rodriguez E,Hu Z,Ou S,Volchegursky Y,Hutchinson CR,McDaniel R




Has Abstract


2003-08-01 00:00:00












  • Engineering Yarrowia lipolytica for the production of cyclopropanated fatty acids.

    abstract::Traditional synthesis of biodiesel competes with food sources and has limitations with storage, particularly due to limited oxidative stability. Microbial synthesis of lipids provides a platform to produce renewable fuel with improved properties from various renewable carbon sources. Specifically, biodiesel properties...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Markham KA,Alper HS

    更新日期:2018-10-01 00:00:00

  • A microplate spectrofluorometric assay for bacterial biofilms.

    abstract::A spectrofluorometric assay was developed for quantification of bacterial biofilms grown on a microtiter plate. The method involved staining biofilms formed by gram-negative and gram-positive bacteria with wheat germ agglutinin-Alexa Fluor 488 conjugate, which selectively binds to N-acetylglucosamine residues in biofi...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Burton E,Yakandawala N,LoVetri K,Madhyastha MS

    更新日期:2007-01-01 00:00:00

  • Influence of straw types and nitrogen sources on mushroom composting emissions and compost productivity.

    abstract::The effects of different straw types and organic and inorganic nitrogen (N) sources on the chemical composition and odor concentration (OC) of mushroom composting emissions, compost parameters, and mushroom yield were examined using bench-scale and large-scale (windrows and aerated tunnels) composting systems. There w...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Noble R,Hobbs PJ,Mead A,Dobrovin-Pennington A

    更新日期:2002-09-01 00:00:00

  • Assessment of physiological state of microorganisms in activated sludge with flow cytometry: application for monitoring sludge production minimization.

    abstract::Many sludge reduction processes have been studied for the minimization of sludge production in biological wastewater treatment. The investigations on most of these processes have monitored the increase of the soluble chemical oxygen demand, the sludge mass reduction, or the decrease of the floc size, but little inform...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Prorot A,Eskicioglu C,Droste R,Dagot C,Leprat P

    更新日期:2008-11-01 00:00:00

  • Evaluation of liquid and solid culture media for the recovery and enrichment of Burkholderia cenocepacia from distilled water.

    abstract::Burkholderia cepacia complex (BCC) presence has been the cause of recalls of both sterile and non-sterile pharmaceutical products since these opportunistic pathogens have been implicated to cause infections to susceptible individuals. BCC are ubiquitous in nature, but in pharmaceutical settings the most common source ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Ahn Y,Kim JM,Ahn H,Lee YJ,LiPuma JJ,Hussong D,Cerniglia CE

    更新日期:2014-07-01 00:00:00

  • Five gene products are required for assembly of the central pyrrole moiety of coumermycin A1.

    abstract::Coumermycin A1 is an aminocoumarin antibiotic produced by Streptomyces rishiriensis. It exhibits potent antibacterial and anticancer activity. The coumermycin A1 molecule contains two terminal 5-methyl-pyrrole-2-carboxylic acid moieties and one central 3-methylpyrrole-2,4-dicarboxylic acid moiety (CPM). While the bios...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Novotna J,Gust B,Kulik A,Spizek J,Heide L

    更新日期:2013-08-01 00:00:00

  • Current approaches to exploit actinomycetes as a source of novel natural products.

    abstract::For decades, microbial natural products have been one of the major sources of novel drugs for pharmaceutical companies, and today all evidence suggests that novel molecules with potential therapeutic applications are still waiting to be discovered from these natural sources, especially from actinomycetes. Any appropri...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章,评审


    authors: Genilloud O,González I,Salazar O,Martín J,Tormo JR,Vicente F

    更新日期:2011-03-01 00:00:00

  • Engineering of Rhodococcus cell catalysts for tolerance improvement by sigma factor mutation and active plasmid partition.

    abstract::Tolerance to various stresses is a key phenotype for cell catalysts, which are used widely in bioproduction of diverse valuable chemicals. Using the Rhodococcus ruber TH strain, which exhibits high nitrile hydratase activity, as the target cell catalyst for acrylamide production, we established a method to improve cel...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Ma Y,Yu H

    更新日期:2012-10-01 00:00:00

  • Eicosapentaenoic and docosahexaenoic acids production by and okara-utilizing potential of thraustochytrids.

    abstract::Nine thraustochytrid strains isolated from subtropical mangroves were screened for their eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) production potential in a glucose yeast extract medium. Their ability to utilize okara (soymilk residue) for growth and EPA and DHA production was also evaluated. EPA yiel...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Fan KW,Chen F,Jones EB,Vrijmoed LL

    更新日期:2001-10-01 00:00:00

  • Phytostimulation and biofertilization in wheat by cyanobacteria.

    abstract::Cyanobacteria are commonly used for the phytostimulation and biofertilization of agriculture crops due to their nitrogen-fixing ability. However, the contribution by their phytohormones has been neglected. This study focuses on the screening of rhizospheric and free-living cyanobacteria for in vitro phytohormones prod...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Hussain A,Hasnain S

    更新日期:2011-01-01 00:00:00

  • Identification of metabolites produced from N-phenylpiperazine by Mycobacterium spp.

    abstract::Mycobacterium sp. 7E1B1W and seven other mycobacterial strains known to degrade hydrocarbons were investigated to determine their ability to metabolize the piperazine ring, a substructure found in many drugs. Cultures were grown at 30 degrees C in tryptic soy broth and dosed with 3.1 mM N-phenylpiperazine hydrochlorid...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Adjei MD,Deck J,Heinze TM,Freeman JP,Williams AJ,Sutherland JB

    更新日期:2007-03-01 00:00:00

  • A comparison of stress tolerance in YPD and industrial lignocellulose-based medium among industrial and laboratory yeast strains.

    abstract::In general, it is believed that fermentation by yeast under harsh industrial conditions, especially if substrates such as wood hydrolysate or lignocellulosic substrates are used, requires the use of so-called industrial strains. In order to check whether this is always true, a comparison of performance was made using ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Albers E,Larsson C

    更新日期:2009-08-01 00:00:00

  • Engineering of isoamylase: improvement of protein stability and catalytic efficiency through semi-rational design.

    abstract::Isoamylase catalyzes the hydrolysis of α-1,6-glycosidic linkages in glycogen, amylopectin and α/β-limit dextrins. A semi-rational design strategy was performed to improve catalytic properties of isoamylase from Bacillus lentus. Three residues in vicinity of the essential residues, Arg505, Asn513, and Gly608, were chos...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Li Y,Zhang L,Ding Z,Gu Z,Shi G

    更新日期:2016-01-01 00:00:00

  • Tobermolite effects on methane removal activity and microbial community of a lab-scale soil biocover.

    abstract::Three identical lab-scale biocovers were packed with an engineered soil (BC 1), tobermolite only (BC 2), and a mixture of the soil and tobermolite (BC 3), and were operated at an inlet load of 338-400 g-CH4 m(-2) d(-1) and a space velocity of 0.12 h(-1). The methane removal capacity was 293 ± 47 g-CH4 m(-2) d(-1) in s...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Moon KE,Lee EH,Kim TG,Cho KS

    更新日期:2014-07-01 00:00:00

  • The carboxylic acid reduction pathway in Nocardia. Purification and characterization of the aldehyde reductase.

    abstract::Whole cultures of Nocardia sp. NRRL 5646 reduce carboxylic acids, first to aldehydes, then to alcohols and subsequently to the corresponding acetyl esters. This work describes an NADPH-dependent reductase responsible for catalyzing the reduction of aldehyde intermediates, which was purified 3240-fold by a combination ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Li T,Rosazza JP

    更新日期:2000-12-01 00:00:00

  • Detection of non-host viable contaminants in Pichia pastoris cultures and fermentation broths.

    abstract::The ability to detect viable contaminants in cultures propagated from the original host-expression system ensures that the integrity and purity of seed banks, fermentation broths, and ultimately the final product are continually controlled and maintained. The method developed to detect such agents must be selective fo...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Plantz BA,Andersen J,Smith LA,Meagher MM,Schlegel VL

    更新日期:2003-11-01 00:00:00

  • Identification and characterization of a novel cold-adapted esterase from a metagenomic library of mountain soil.

    abstract::A novel lipolytic enzyme was isolated from a metagenomic library after demonstration of lipolytic activity on an LB agar plate containing 1% (w/v) tributyrin. A novel esterase gene (estIM1), encoding a lipolytic enzyme (EstIM1), was cloned using a shotgun method from a pFosEstIM1 clone of the metagenomic library, and ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Ko KC,Rim SO,Han Y,Shin BS,Kim GJ,Choi JH,Song JJ

    更新日期:2012-05-01 00:00:00

  • Production and genetic improvement of a novel antimycotic agent, saadamycin, against dermatophytes and other clinical fungi from endophytic Streptomyces sp. Hedaya48.

    abstract::As a part of our ongoing efforts towards finding novel antimycotic agents from marine microflora of the Red Sea, vanillin, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and the new antimycotic compound saadamycin were isolated from endophytic Streptomyces sp. Hedaya48. The producing strain was isolated from the Egyptian sp...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: El-Gendy MM,El-Bondkly AM

    更新日期:2010-08-01 00:00:00

  • Enhanced poly-γ-L-diaminobutanoic acid production in Bacillus pumilus by combining genome shuffling with multiple antibiotic-resistance.

    abstract::A breeding approach combining genome shuffling with multiple antibiotic-resistance including gentamicin, rifampin and lincomycin, was developed in this research to improve the poly-γ-L-diaminobutanoic acid (γ-PAB) production in Bacillus pumilus LS-1. By this unique strategy, recombinants from the third round of genome...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Li S,Wang L,Wang N

    更新日期:2020-12-01 00:00:00

  • Recombinant Escherichia coli engineered for production of L-lactic acid from hexose and pentose sugars.

    abstract::Recombinant Escherichia coli have been constructed for the conversion of glucose as well as pentose sugars into L-lactic acid. The strains carry the lactate dehydrogenase gene from Streptococcus bovis on a low copy number plasmid for production of L-lactate. Three E. coli strains were transformed with the plasmid for ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Dien BS,Nichols NN,Bothast RJ

    更新日期:2001-10-01 00:00:00

  • Bioprocess for efficient production of recombinant Pichia anomala phytase and its applicability in dephytinizing chick feed and whole wheat flat Indian breads.

    abstract::The phytase of the yeast Pichia anomala (PPHY) is a suitable biocatalyst as a food and feed additive because of its adequate thermostability, acid stability, protease insensitivity and broad substrate spectrum. The cell-bound nature and low phytase titres are the main bottlenecks for its utility in food and feed indus...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Joshi S,Satyanarayana T

    更新日期:2015-10-01 00:00:00

  • Mechanism of proanthocyanidins-induced alcoholic fermentation enhancement in Saccharomyces cerevisiae.

    abstract::Our previous work revealed proanthocyanidins (PAs) could pose significant enhancement on the activity of H(+)-ATPase and fermentation efficiency after a transient initial inhibition (Li et al in Am J Enol Vitic 62(4):512-518, 2011). The aim of the present work was to understand the possible mechanism for this regulati...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Li J,Zhao H,Huang W

    更新日期:2014-12-01 00:00:00

  • The effect of albumin fusion structure on the production and bioactivity of the somatostatin-28 fusion protein in Pichia pastoris.

    abstract::Somatostatin, a natural inhibitor of growth hormone (GH), and its analogs have been used in clinical settings for the treatment of acromegaly, gigantism, thyrotropinoma, and other carcinoid syndromes. However, natural somatostatin is limited for clinical usage because of its short half-life in vivo. Albumin fusion tec...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Ding Y,Fan J,Li W,Peng Y,Yang R,Deng L,Fu Q

    更新日期:2014-06-01 00:00:00

  • Metabolic engineering of Corynebacterium glutamicum for improved L-arginine synthesis by enhancing NADPH supply.

    abstract::Corynebacterium glutamicum SNK 118 was metabolically engineered with improved L-arginine titer. Considering the crucial role of NADPH level in L-arginine production, pntAB (membrane-bound transhydrogenase) and ppnK (NAD+ kinase) were co-expressed to increase the intracellular NADPH pool. Expression of pntAB exhibited ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Zhan M,Kan B,Dong J,Xu G,Han R,Ni Y

    更新日期:2019-01-01 00:00:00

  • Improvement of bioremediation by Pseudomonas and Burkholderia by mutants of the Vitreoscilla hemoglobin gene (vgb) integrated into their chromosomes.

    abstract::Using genetic engineering, the Vitreoscilla (bacterial) hemoglobin gene (vgb) was integrated stably into the chromosomes of Pseudomonas aeruginosa and Burkholderia sp. strain DNT. This was done for both wild type vgb and two site-directed mutants of vgb that produce Vitreoscilla hemoglobin (VHb) with lowered oxygen af...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Kim Y,Webster DA,Stark BC

    更新日期:2005-04-01 00:00:00

  • Deletion of PHO13 improves aerobic L-arabinose fermentation in engineered Saccharomyces cerevisiae.

    abstract::Pentose sugars are increasingly being used in industrial applications of Saccharomyces cerevisiae. Although L-arabinose is a highlighted pentose that has been identified as next-generation biomass, arabinose fermentation has not yet undergone extensive development for industrial utilization. In this study, we integrat...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Ye S,Jeong D,Shon JC,Liu KH,Kim KH,Shin M,Kim SR

    更新日期:2019-12-01 00:00:00

  • Identification of Geotrichum candidum at the species and strain level: proposal for a standardized protocol.

    abstract::In this study, the M13 primer was used to distinguish Geotrichum candidum from the anamorphic and teleomorphic forms of other arthrospore-forming species (discriminatory power = 0.99). For intraspecific characterization, the GATA4 primer showed the highest level of discrimination for G. candidum among the 20 microsate...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Gente S,Sohier D,Coton E,Duhamel C,Gueguen M

    更新日期:2006-12-01 00:00:00

  • A simulation study comparing the impact of experimental error on the performance of experimental designs and artificial neural networks used for process screening.

    abstract::Many variables and their interactions can affect a biotechnological process. Testing a large number of variables and all their possible interactions is a cumbersome task and its cost can be prohibitive. Several screening strategies, with a relatively low number of experiments, can be used to find which variables have ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Soria MA,Gonzalez Funes JL,Garcia AF

    更新日期:2004-11-01 00:00:00

  • Discovery of a new diol-containing polyketide by heterologous expression of a silent biosynthetic gene cluster from Streptomyces lavendulae FRI-5.

    abstract::The genome of streptomycetes has the ability to produce many novel and potentially useful bioactive compounds, but most of which are not produced under standard laboratory cultivation conditions and are referred to as silent/cryptic secondary metabolites. Streptomyces lavendulae FRI-5 produces several types of bioacti...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Pait IGU,Kitani S,Roslan FW,Ulanova D,Arai M,Ikeda H,Nihira T

    更新日期:2018-02-01 00:00:00

  • Selection of an autochthonous Saccharomyces strain starter for alcoholic fermentation of Sherry base wines.

    abstract::Several indigenous Saccharomyces strains from musts were isolated in the Jerez de la Frontera region, at the end of spontaneous fermentation, in order to select the most suitable autochthonous yeast starter, during the 2007 vintage. Five strains were chosen for their oenological abilities and fermentative kinetics to ...

    journal_title:Journal of industrial microbiology & biotechnology

    pub_type: 杂志文章


    authors: Rodríguez-Palero MJ,Fierro-Risco J,Codón AC,Benítez T,Valcárcel MJ

    更新日期:2013-06-01 00:00:00