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Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis

Microbial synthesis of valuable hemoproteins has become a popular research topic, and Pichia pastoris is a versatile platform for the industrial production of recombinant proteins. However, the inadequate supply of heme limits the synthesis of high‐active hemoproteins. Here a strategy for enhancing...

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Autores principales: Yu, Fei, Zhao, Xinrui, Zhou, Jingwen, Lu, Wei, Li, Jianghua, Chen, Jian, Du, Guocheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602571/
https://www.ncbi.nlm.nih.gov/pubmed/37649147
http://dx.doi.org/10.1002/advs.202302826
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author Yu, Fei
Zhao, Xinrui
Zhou, Jingwen
Lu, Wei
Li, Jianghua
Chen, Jian
Du, Guocheng
author_facet Yu, Fei
Zhao, Xinrui
Zhou, Jingwen
Lu, Wei
Li, Jianghua
Chen, Jian
Du, Guocheng
author_sort Yu, Fei
collection PubMed
description Microbial synthesis of valuable hemoproteins has become a popular research topic, and Pichia pastoris is a versatile platform for the industrial production of recombinant proteins. However, the inadequate supply of heme limits the synthesis of high‐active hemoproteins. Here a strategy for enhancing intracellular heme biosynthesis to improve the titers and functional activities of hemoproteins is reported. After selecting a suitable expressional strategy for globins, the efficient heme‐supply P. pastoris chassis is established by removing the spatial segregation during heme biosynthesis, optimizing precursor synthesis, assembling rate‐limiting enzymes using protein scaffolds, and inhibiting heme degradation. This robust chassis produces several highly active hemoproteins, including porcine myoglobin, soy hemoglobin, Vitreoscilla hemoglobin, and P450‐BM3, which can be used in the development of artificial meat, high‐cell‐density fermentation, and whole‐cell catalytic synthesis of high‐value‐added compounds. Furthermore, the engineered chassis strain has great potential for producing and applying other hemoproteins with high activities in various fields.
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spelling pubmed-106025712023-10-27 Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis Yu, Fei Zhao, Xinrui Zhou, Jingwen Lu, Wei Li, Jianghua Chen, Jian Du, Guocheng Adv Sci (Weinh) Research Articles Microbial synthesis of valuable hemoproteins has become a popular research topic, and Pichia pastoris is a versatile platform for the industrial production of recombinant proteins. However, the inadequate supply of heme limits the synthesis of high‐active hemoproteins. Here a strategy for enhancing intracellular heme biosynthesis to improve the titers and functional activities of hemoproteins is reported. After selecting a suitable expressional strategy for globins, the efficient heme‐supply P. pastoris chassis is established by removing the spatial segregation during heme biosynthesis, optimizing precursor synthesis, assembling rate‐limiting enzymes using protein scaffolds, and inhibiting heme degradation. This robust chassis produces several highly active hemoproteins, including porcine myoglobin, soy hemoglobin, Vitreoscilla hemoglobin, and P450‐BM3, which can be used in the development of artificial meat, high‐cell‐density fermentation, and whole‐cell catalytic synthesis of high‐value‐added compounds. Furthermore, the engineered chassis strain has great potential for producing and applying other hemoproteins with high activities in various fields. John Wiley and Sons Inc. 2023-08-30 /pmc/articles/PMC10602571/ /pubmed/37649147 http://dx.doi.org/10.1002/advs.202302826 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Yu, Fei
Zhao, Xinrui
Zhou, Jingwen
Lu, Wei
Li, Jianghua
Chen, Jian
Du, Guocheng
Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis
title Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis
title_full Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis
title_fullStr Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis
title_full_unstemmed Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis
title_short Biosynthesis of High‐Active Hemoproteins by the Efficient Heme‐Supply Pichia Pastoris Chassis
title_sort biosynthesis of high‐active hemoproteins by the efficient heme‐supply pichia pastoris chassis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602571/
https://www.ncbi.nlm.nih.gov/pubmed/37649147
http://dx.doi.org/10.1002/advs.202302826
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