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Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene
INTRODUCTION: Red-colored lycopene has received remarkable attention in medicine because of its antioxidant properties for reducing the risks of many human cancers. However, the extraction of lycopene from natural hosts is limited. Moreover, the chemically synthesized lycopene raises safety concerns...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885113/ https://www.ncbi.nlm.nih.gov/pubmed/36726563 http://dx.doi.org/10.3389/fmicb.2022.1100745 |
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author | Su, Qixuan Cheng, Ping Sun, Jiyuan Zhang, Yulin Zheng, Yang Jiang, Xiao-Ran Rao, Xiancai |
author_facet | Su, Qixuan Cheng, Ping Sun, Jiyuan Zhang, Yulin Zheng, Yang Jiang, Xiao-Ran Rao, Xiancai |
author_sort | Su, Qixuan |
collection | PubMed |
description | INTRODUCTION: Red-colored lycopene has received remarkable attention in medicine because of its antioxidant properties for reducing the risks of many human cancers. However, the extraction of lycopene from natural hosts is limited. Moreover, the chemically synthesized lycopene raises safety concerns due to residual chemical reagents. Halomonas bluephagenesis is a versatile chassis for the production of fine chemicals because of its open growth property without sterilization. METHODS: A heterologous mevalonate (MVA) pathway was introduced into H. bluephagenesis strain TD1.0 to engineer a bacterial host for lycopene production. A pTer7 plasmid mediating the expression of six MVA pathway genes under the control of a phage P(Mmp1) and an Escherichia coli P(trc) promoters and a pTer3 plasmid providing lycopene biosynthesis downstream genes derived from Streptomyces avermitilis were constructed and transformed into TD1.0. The production of lycopene in the engineered H. bluephagenesis was evaluated. Optimization of engineered bacteria was performed to increase lycopene yield. RESULTS: The engineered TD1.0/pTer7-pTer3 produced lycopene at a maximum yield of 0.20 mg/g dried cell weight (DCW). Replacing downstream genes with those from S. lividans elevated the lycopene production to 0.70 mg/g DCW in the TD1.0/pTer7-pTer5 strain. Optimizing the P(Mmp1) promoter in plasmid pTer7 with a relatively weak P(trc) even increased the lycopene production to 1.22 mg/g DCW. However, the change in the P(trc) promoter in pTer7 with P(Mmp1) did not improve the yield of lycopene. CONCLUSION: We first engineered an H. bluephagenesis for the lycopene production. The co-optimization of downstream genes and promoters governing MVA pathway gene expressions can synergistically enhance the microbial overproduction of lycopene. |
format | Online Article Text |
id | pubmed-9885113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98851132023-01-31 Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene Su, Qixuan Cheng, Ping Sun, Jiyuan Zhang, Yulin Zheng, Yang Jiang, Xiao-Ran Rao, Xiancai Front Microbiol Microbiology INTRODUCTION: Red-colored lycopene has received remarkable attention in medicine because of its antioxidant properties for reducing the risks of many human cancers. However, the extraction of lycopene from natural hosts is limited. Moreover, the chemically synthesized lycopene raises safety concerns due to residual chemical reagents. Halomonas bluephagenesis is a versatile chassis for the production of fine chemicals because of its open growth property without sterilization. METHODS: A heterologous mevalonate (MVA) pathway was introduced into H. bluephagenesis strain TD1.0 to engineer a bacterial host for lycopene production. A pTer7 plasmid mediating the expression of six MVA pathway genes under the control of a phage P(Mmp1) and an Escherichia coli P(trc) promoters and a pTer3 plasmid providing lycopene biosynthesis downstream genes derived from Streptomyces avermitilis were constructed and transformed into TD1.0. The production of lycopene in the engineered H. bluephagenesis was evaluated. Optimization of engineered bacteria was performed to increase lycopene yield. RESULTS: The engineered TD1.0/pTer7-pTer3 produced lycopene at a maximum yield of 0.20 mg/g dried cell weight (DCW). Replacing downstream genes with those from S. lividans elevated the lycopene production to 0.70 mg/g DCW in the TD1.0/pTer7-pTer5 strain. Optimizing the P(Mmp1) promoter in plasmid pTer7 with a relatively weak P(trc) even increased the lycopene production to 1.22 mg/g DCW. However, the change in the P(trc) promoter in pTer7 with P(Mmp1) did not improve the yield of lycopene. CONCLUSION: We first engineered an H. bluephagenesis for the lycopene production. The co-optimization of downstream genes and promoters governing MVA pathway gene expressions can synergistically enhance the microbial overproduction of lycopene. Frontiers Media S.A. 2023-01-16 /pmc/articles/PMC9885113/ /pubmed/36726563 http://dx.doi.org/10.3389/fmicb.2022.1100745 Text en Copyright © 2023 Su, Cheng, Sun, Zhang, Zheng, Jiang and Rao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Su, Qixuan Cheng, Ping Sun, Jiyuan Zhang, Yulin Zheng, Yang Jiang, Xiao-Ran Rao, Xiancai Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene |
title | Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene |
title_full | Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene |
title_fullStr | Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene |
title_full_unstemmed | Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene |
title_short | Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene |
title_sort | engineering a mevalonate pathway in halomonas bluephagenesis for the production of lycopene |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885113/ https://www.ncbi.nlm.nih.gov/pubmed/36726563 http://dx.doi.org/10.3389/fmicb.2022.1100745 |
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