• Journal of the Korean Operations Research and Management Science Society
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• v.32 no.1
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• pp.93-104
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• 2007

We consider a supply chain where products are shipped to warehouse from manufacturing system to customers. Products are supplied from either in-house regular manufacturing or the secondary source such as subcontractor. The inventory in warehouse is controlled by base-stock policy, that is, whenever a demand arrives from customer, an order is released to the manufacturing system. Unsatisfied demand is backlogged. The manufacturing system is modeled as M/M/s+1/c queueing system, and the orders exceeding the given limit care blocked and lost. The steady state distribution of the outstanding orders and the throughput of the manufacturing system are functions of the level of engagement In the secondary source. There is a profit obtained from throughput and cost not only due to the engagement of the secondary source in the manufacturing system but also inventory positions. We want to maximize the total production profit minus the total cost of the production system by simultaneously determining the optimal level of engagement of the secondary source and the optimal base-stock level of the inventory. We develop two algorithms : one without guarantee of the optimal solution but with the small number of computations, the other optimal but with more computations.

• 한국생물공학회:학술대회논문집
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• 2000.04a
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• pp.267-270
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• 2000

In general, pigment production can be influenced by the medium composition, pH and physical factors such as aeration, agitation, and visible light. The influence of gaseous environments on the pigment production by Monascus purpureus ATCC 16365 was investigated by controlling the DO (dissolved oxygen) concentration through aeration and agitation. When the DO concentration was controlled below 20%, the production of red pigment significantly increased whereas the biomass production decreased. Therefore, the dissolved oxygen concentration could significantly affect the biosynthesis of red pigment as a secondary metabolite by a wild-type filamentous fungus under the anaerobic condition. The results indicate a high potential of enhancing the productivity of the red pigment as a secondary metabolite through controlling the DO concentration.

• Microbiology and Biotechnology Letters
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• v.22 no.5
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• pp.459-466
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• 1994

Virginiae butanolide C(VB-C) is one of the butyrolactone autoregulators, which triggers the production of virginiamycin in Streptomyces virginiae. Streptomyces longwoodensis was selected as a test strain to investigate new VB-C functions. When 100 ng/ml of the synthetic VB-C was added into the culture at 5 hour and 0 hour, the initial production time of antibiotics and a dark blue pigment were shortened by 4~6 hours and 2~4 hours, respectively. HPLC analysis revealed the production of several new antibiotics by VB-C addition. In the SDS-PAGE analysis of the total protein from mycelium several new protein bands showed up and the amounts of certain protein bands increased in the presense of VB-C. The existence of specific VB-C binding protein was confirmed from S. longwoodensis in relation to VB-C signal transduction. These results suggest that the VB-C might have an ability to induce the production of secondary metabolites in Streptomy- ces longwoodensis.

• Korean Journal of Microbiology
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• v.28 no.4
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• pp.318-323
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• 1990

The bacterial secondary production was measured at 6 sites of Lake Soyang in October, 1989 by $^{3}$H-thymidine incorporation rate. Verfication for the method of bacterial secondary production measurement showed that $^{3}$H-thymidine incorporated into DNA, RNA and protein by average percentage of 38.45, 42.27 and 20.07%, respectively. THe more increased incoporated $^{3}$H-thymidine, the more increasde DNA fraction, but protein fraction was generally low. Incorporation of rate of /usp 3/H-thymidine. $^{3}$H-leucine into protein correlated with protein fraction of incorporated $^{3}$H-thymidine. Conversion factors were calculated as follows; $1.83*10 ^{20}$ cells/moles of thymidine incorporated/hr and 1.69*10$^{22}$ cells/moles of leucine incorporated/hr.

• Journal of Microbiology and Biotechnology
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• v.17 no.11
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• pp.1818-1825
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• 2007

S-Adenosylmethionine (SAM) was previously documented to activate secondary metabolism in a variety of Streptomyces spp. and to promote actinorhodin (ACT) and undecylprodigiosin (RED) in Streptomyces coelicolor. The SAM-induced proteins in S. coelicolor include several ABC transporter components (SCO5260 and SCO5477) including BldKB, the component of a well-known regulatory factor for differentiations. In order to assess the role of these ABC transporter complexes in differentiation of Streptomyces, SCO5260 and SCO5476, the first genes from the cognate complex clusters, were individually inactivated by gene replacement. Inactivation of either SCO5260 or SCO5476 led to impaired sporulation on agar medium, with the more drastic defect in the SCO5260 null mutant (${\Delta}SCO5260$). ${\Delta}SCO5260$ displayed growth retardation and reduced yields of ACT and RED in liquid cultures. In addition, SAM supplementation failed in promoting the production of ACT and RED in ${\Delta}SCO5260$. Inactivation of SCO5476 gave no significant change in growth and production of ACT and RED, but impaired the promoting effect of SAM on ACT production without interfering with the effect on RED production. The present study suggests that SAM induces several ABC transporters to modulate secondary metabolism and morphological development in S. coelicolor.

• Journal of Microbiology and Biotechnology
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• v.24 no.6
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• pp.823-834
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• 2014

In order to solve the shortage of natural Tripterygium wilfordii Hook. f. plant resource for the production of the important secondary metabolites triptolide and wilforine, hairy roots were induced from its root calli by Agrobacterium rhizogenes. Induced hairy roots not only could be maintained and grown well in hormone-free half-strength Murashige and Skoog medium but also could produce sufficient amounts of both triptolide and wilforine. Although hairy roots produced approximately 15% less triptolide than adventitious roots and 10% less wilforine than naturally grown roots, they could grow fast and could be a suitable system for producing both secondary metabolites compared with other tissues. Addition of $50{\mu}M$ methyl jasmonate (MeJA) could slightly affect hairy root growth, but dramatically stimulated the production of both triptolide and wilforine, whereas $50{\mu}M$ salicylic acid had no apparent effect on hairy root growth with slightly stimulatory effects on the production of both secondary metabolites. Addition of precursor nicotinic acid, isoleucine, or aspartic acid at the concentration of $500{\mu}M$ had varying effects on hairy root growth, but none of them had stimulatory effects on triptolide production, and only the former two had slightly beneficial effects on wilforine production. The majority of triptolide produced was secreted into the medium, whereas most of the produced wilforine was retained inside of hairy roots. Our studies provide a promising way to produce triptolide and wilforine in T. wilfordii hairy root cultures combined with MeJA treatment.

• Journal of Plant Biotechnology
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• v.30 no.3
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• pp.301-305
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• 2003

The effects of inorganic nitrogen sources such as KNO$_3$ and NH$_4$ NO$_3$ on cell growth and production of chlorogenic acid and eleutheroside E derivative were investigated in 5L bioreactor cultures of Eleutherococcus senticosus. The cell growth in the 1/2MS medium containing 15mMKNO$_{3}$. The fresh weight of cells harvested from bioreactor was affected by the concentration ratio of NO$_3$$^{[-10]}$ and NH$_4$$^{+}$ in culture medium. At the viewpoint of secondary metabolite production, the production of chlorogenic acid was affected by the concentration of NH$_4$$^{+}$ in the culture medium, but not by the total concentration of nitrogen sources in the culture medium. Futhermore, eleutheroside E derivative production was also affected by the concentration ratio of NO$_3$$^{[-10]}$ and NH$_4$$^{+}$ in the culture medium. Base on those results, it is suggested that cell growth and production of secondary metabolite(chlorogenic acid and eleutheroside E derivative) could be manipulated by controlling the total concentration of nitrogen sources and the concentration ratio of NO$_3$$^{[-10]}$ and NH$_4$$^{+}$ in the culture medium. medium.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.3
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• pp.138-149
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• 2002

Plant cell culture provides a viable alternative over whole plant cultivation for the production of secondary metabolites. In order to successfully cultivate the plant cells at large scale, several engineering parameters such as, cell aggregation, mixing, aeration, and shear sensitivity are taken into account for selection of a suitable bioreactor. The media ingredients, their concentrations and the environmental factors are optimized for maximal synthesis of a desired metabolite. Increased productivity in a bioreactor can be achieved by selection of a proper cultivation strategy (batch, fed-batch, two-stage etc.), feeding of metabolic precursors and extraction of intracellular metabolites. Proper understanding and rigorous analysis of these parameters would pave the way towards the successful commercialization of plant cell bioprocesses.

• 한국균학회소식:학술대회논문집
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• 2018.05a
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• pp.51-51
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• 2018

The application of recombinant DNA technology has been remarkable and nearly replaced commonly used traditional methods. Traditional industrial microbiology long depended on the discovery of valuable strains and mutagenesis of such strains to improve its secretion capacity of enzymes and secondary metabolites on the industrial scale. Commodities included industrial enzymes and biopharmaceuticals. The purpose of genome manipulation by the crossing of different strains or genetic recombination of naked DNA to the genome is of increased production of valuable metabolites. We optimized a transformation method to either for removal of innate genes, introduction of heterologous genes, or combination of both. We have been used selected whole or partial genes to manipulate target fungi toward the development of strains overproducing invaluable proteins. We have also used the whole genome sequence information of fungal genomes in public databases and functional genomics approach to select genes to manipulate and eventually contributing greatly to the development of overproducing industrial strains overproducing proteins or secondary metabolites. I will briefly review 1) filamentous fungi as a host for production of recombinant proteins and secondary metabolites, 2) markets of industrial metabolites, 3) a new approach to manipulate up to five genes at the same time in the system that ProxEnrem uses.

• Journal of Microbiology and Biotechnology
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• v.16 no.6
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• pp.821-831
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• 2006

Unicellular green algae of the genus Haematococcus have been studied extensively as model organisms for secondary carotenoid accumulation. Upon environmental stress, such as strong irradiance or nitrogen deficiency, unicellular green algae of the genus Haematococcus accumulate secondary carotenoids in vesicles in the cytosol. Because secondary carotenoid accumulation occurs only upon specific environmental stimuli, there is speculation about the regulation of the biosynthetic pathway specific for secondary carotenogenesis. Because the carotenoid biosynthesis pathway is located both in the chloroplast and the cytosol, communication between both cellular compartments must be considered. Recently, the induction and regulation of astaxanthin biosynthesis in microalgae received considerable attention because of the increasing use of this secondary carotenoid as a source of pigmentation for fish aquaculture, as a component in cancer prevention, and as a free-radical quencher. This review summarizes the biosynthesis and regulation of the pathway, as well as the biotechnology of astaxanthin production in Haematococcus.