Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris

Human is an essential cellular enzymethat is found in all human cells. As this enzyme is upregulated in cancer cells exceedingly, it is used as a target for cancer chemotherapeutic drug development. As such, producing the in-house enzyme for the purpose to speed up the search for more cost-effecti...

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Main Authors: Ruo, Ping Ang, Leong, Sin Teoh, Mooi, Kwai Chana, Miswan, Noorizan, Boon, Yin Khoo
Format: Article
Published: Elsevier 2016
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Online Access:http://eprints.usm.my/36835/
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author Ruo, Ping Ang
Leong, Sin Teoh
Mooi, Kwai Chana
Miswan, Noorizan
Boon, Yin Khoo
author_facet Ruo, Ping Ang
Leong, Sin Teoh
Mooi, Kwai Chana
Miswan, Noorizan
Boon, Yin Khoo
author_sort Ruo, Ping Ang
building USM Institutional Repository
collection Online Access
description Human is an essential cellular enzymethat is found in all human cells. As this enzyme is upregulated in cancer cells exceedingly, it is used as a target for cancer chemotherapeutic drug development. As such, producing the in-house enzyme for the purpose to speed up the search for more cost-effective and target specific hTopoI inhibitors is warranted. This study aims to compare the optimised conditions for the expression of hTopoI in KM71H (MutS) and X33 (Mut+) strains of Pichia pastoris. P. pastoris transfected with an hTopoI recombinant vector was used for the optimization of a higher level of hTopoI expression. Results: In the process, fed-batch cultivation parameters that influence the expression of hTopoI, such as culture temperature, methanol induction and feeding strategy, were optimised in the transfected KM71H and X33 P. pastoris strains in a shake flask system. The cell density and total protein concentration (protein level) of transfected P. pastoris were compared to determine the optimum culture conditions for each transfected P. pastoris strain. A higher hTopoI level was observed in the transfected KM71H culture supernatant (2.26 ng/mL) when the culture was incubated in the optimum conditions. Conclusions: This study demonstrated thatMutS strain (KM71H) expressed and secreted a higher level of hTopoI heterologous protein in the presence of methanol compared to the Mut+ strain; X33 (0.75 ng/mL). However, other aspects of optimization, such as pH, should also be considered in the future, to obtain the optimum expression level of hTopoI in P. pastoris.
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spelling usm-368352017-09-29T07:12:18Z http://eprints.usm.my/36835/ Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris Ruo, Ping Ang Leong, Sin Teoh Mooi, Kwai Chana Miswan, Noorizan Boon, Yin Khoo R735-854 Medical education. Medical schools. Research T1-995 Technology(General) Human is an essential cellular enzymethat is found in all human cells. As this enzyme is upregulated in cancer cells exceedingly, it is used as a target for cancer chemotherapeutic drug development. As such, producing the in-house enzyme for the purpose to speed up the search for more cost-effective and target specific hTopoI inhibitors is warranted. This study aims to compare the optimised conditions for the expression of hTopoI in KM71H (MutS) and X33 (Mut+) strains of Pichia pastoris. P. pastoris transfected with an hTopoI recombinant vector was used for the optimization of a higher level of hTopoI expression. Results: In the process, fed-batch cultivation parameters that influence the expression of hTopoI, such as culture temperature, methanol induction and feeding strategy, were optimised in the transfected KM71H and X33 P. pastoris strains in a shake flask system. The cell density and total protein concentration (protein level) of transfected P. pastoris were compared to determine the optimum culture conditions for each transfected P. pastoris strain. A higher hTopoI level was observed in the transfected KM71H culture supernatant (2.26 ng/mL) when the culture was incubated in the optimum conditions. Conclusions: This study demonstrated thatMutS strain (KM71H) expressed and secreted a higher level of hTopoI heterologous protein in the presence of methanol compared to the Mut+ strain; X33 (0.75 ng/mL). However, other aspects of optimization, such as pH, should also be considered in the future, to obtain the optimum expression level of hTopoI in P. pastoris. Elsevier 2016-05 Article PeerReviewed Ruo, Ping Ang and Leong, Sin Teoh and Mooi, Kwai Chana and Miswan, Noorizan and Boon, Yin Khoo (2016) Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris. Electronic Journal of Biotechnology, 21. pp. 9-17. ISSN 0717-3458 http://dx.doi.org/10.1016/j.ejbt.2016.01.007
spellingShingle R735-854 Medical education. Medical schools. Research
T1-995 Technology(General)
Ruo, Ping Ang
Leong, Sin Teoh
Mooi, Kwai Chana
Miswan, Noorizan
Boon, Yin Khoo
Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris
title Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris
title_full Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris
title_fullStr Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris
title_full_unstemmed Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris
title_short Comparing the expression of human DNA topoisomerase I in KM71H and X33 strains of Pichia pastoris
title_sort comparing the expression of human dna topoisomerase i in km71h and x33 strains of pichia pastoris
topic R735-854 Medical education. Medical schools. Research
T1-995 Technology(General)
url http://eprints.usm.my/36835/
http://eprints.usm.my/36835/