A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB

Podophyllotoxin (PTOX) is naturally produced by the plant Podophyllum species. Some of its derivatives are anticancer drugs, which are produced mainly by using chemical semi-synthesis methods. Recombinant bacteria have great potential in large-scale production of the derivatives of PTOX. In addition...

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Main Authors: Honglei Liu, Huiyuan Yu, Rui Gao, Fulin Ge, Rui Zhao, Xia Lu, Tianqi Wang, Huaiwei Liu, Chunyu Yang, Yongzhen Xia, Luying Xun
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/13/1/27
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author Honglei Liu
Huiyuan Yu
Rui Gao
Fulin Ge
Rui Zhao
Xia Lu
Tianqi Wang
Huaiwei Liu
Chunyu Yang
Yongzhen Xia
Luying Xun
author_facet Honglei Liu
Huiyuan Yu
Rui Gao
Fulin Ge
Rui Zhao
Xia Lu
Tianqi Wang
Huaiwei Liu
Chunyu Yang
Yongzhen Xia
Luying Xun
author_sort Honglei Liu
collection DOAJ
description Podophyllotoxin (PTOX) is naturally produced by the plant Podophyllum species. Some of its derivatives are anticancer drugs, which are produced mainly by using chemical semi-synthesis methods. Recombinant bacteria have great potential in large-scale production of the derivatives of PTOX. In addition to introducing the correct enzymes, the transportation of PTOX into the cells is an important factor, which limits its modification in the bacteria. Here, we improved the cellular uptake of PTOX into <i>Escherichia coli</i> with the help of the zero-valent sulfur transporter YedE1E2 in the presence of cetyltrimethylammonium bromide (CTAB). CTAB promoted the uptake of PTOX, but induced the production of reactive oxygen species. A protein complex (YedE1E2) of YedE1 and YedE2 enabled <i>E. coli</i> cells to resist CTAB by reducing reactive oxygen species, and YedE1E2 was a hypothetical transporter. Further investigation showed that YedE1E2 facilitated the uptake of extracellular zero-valent sulfur across the cytoplasmic membrane and the formation of glutathione persulfide (GSSH) inside the cells. The increased GSSH minimized oxidative stress. Our results indicate that YedE1E2 is a zero-valent sulfur transporter and it also facilitates CTAB-assisted uptake of PTOX by recombinant bacteria.
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spelling doaj.art-0023de5e67b241ae8c90f16301054ee32024-01-26T14:40:05ZengMDPI AGAntioxidants2076-39212023-12-011312710.3390/antiox13010027A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTABHonglei Liu0Huiyuan Yu1Rui Gao2Fulin Ge3Rui Zhao4Xia Lu5Tianqi Wang6Huaiwei Liu7Chunyu Yang8Yongzhen Xia9Luying Xun10State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, ChinaPodophyllotoxin (PTOX) is naturally produced by the plant Podophyllum species. Some of its derivatives are anticancer drugs, which are produced mainly by using chemical semi-synthesis methods. Recombinant bacteria have great potential in large-scale production of the derivatives of PTOX. In addition to introducing the correct enzymes, the transportation of PTOX into the cells is an important factor, which limits its modification in the bacteria. Here, we improved the cellular uptake of PTOX into <i>Escherichia coli</i> with the help of the zero-valent sulfur transporter YedE1E2 in the presence of cetyltrimethylammonium bromide (CTAB). CTAB promoted the uptake of PTOX, but induced the production of reactive oxygen species. A protein complex (YedE1E2) of YedE1 and YedE2 enabled <i>E. coli</i> cells to resist CTAB by reducing reactive oxygen species, and YedE1E2 was a hypothetical transporter. Further investigation showed that YedE1E2 facilitated the uptake of extracellular zero-valent sulfur across the cytoplasmic membrane and the formation of glutathione persulfide (GSSH) inside the cells. The increased GSSH minimized oxidative stress. Our results indicate that YedE1E2 is a zero-valent sulfur transporter and it also facilitates CTAB-assisted uptake of PTOX by recombinant bacteria.https://www.mdpi.com/2076-3921/13/1/27podophyllotoxinredox oxidative stresssulfane sulfurzero-valent sulfurYedE1E2
spellingShingle Honglei Liu
Huiyuan Yu
Rui Gao
Fulin Ge
Rui Zhao
Xia Lu
Tianqi Wang
Huaiwei Liu
Chunyu Yang
Yongzhen Xia
Luying Xun
A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB
Antioxidants
podophyllotoxin
redox oxidative stress
sulfane sulfur
zero-valent sulfur
YedE1E2
title A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB
title_full A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB
title_fullStr A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB
title_full_unstemmed A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB
title_short A Zero-Valent Sulfur Transporter Helps Podophyllotoxin Uptake into Bacterial Cells in the Presence of CTAB
title_sort zero valent sulfur transporter helps podophyllotoxin uptake into bacterial cells in the presence of ctab
topic podophyllotoxin
redox oxidative stress
sulfane sulfur
zero-valent sulfur
YedE1E2
url https://www.mdpi.com/2076-3921/13/1/27
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