Enhanced Lycopene Productivity by Manipulation of Carbon Flow to Isopentenyl Diphosphate in Escherichia coli
Abstract
Lycopene is a useful phytochemical that holds great commercial value. In our study the lycopene production pathway in E. coli originating from the precursor isopentenyl diphosphate (IPP) of the non‐mevalonate pathway was reconstructed. This engineered strain of E. coli accumulated lycopene intracellularly under aerobic conditions. As a next step, the production of lycopene was enhanced through metabolic engineering methodologies. Various competing pathways at the pyruvate and acetyl‐CoA nodes were inactivated to divert more carbon flux to IPP and subsequently to lycopene. It was found that the ackA‐pta, nuo mutant produced a higher amount of lycopene compared to the parent strain. To further enhance lycopene production, a novel mevalonate pathway, in addition to the already existing non‐mevalonate pathway, was engineered. This pathway utilizes acetyl‐CoA as precursor, condensing it to form acetoacetyl‐CoA and subsequently leading to formation of IPP. Upon the introduction of this new pathway, lycopene production increased by over 2‐fold compared to the ackA‐pta, nuo mutant strain.
Number of times cited: 47
- Seon Young Park, Dongsoo Yang, Shin Hee Ha and Sang Yup Lee, Metabolic Engineering of Microorganisms for the Production of Natural Compounds, Advanced Biosystems, 2, 1, (2017).
- Lijun Ye, Ping He, Qingyan Li, Xueli Zhang and Changhao Bi, Type IIs restriction based combinatory modulation technique for metabolic pathway optimization, Microbial Cell Factories, 16, 1, (2017).
- Nimish Mol Stephen, Gayathri R., R. Niranjana, Yogendra Prasad K., Amit K. Das, Baskaran V. and Ganesan P., Chapter 3 Carotenoids: Types, Sources, and Biosynthesis, Plant Secondary Metabolites, Volume 2, 10.1201/9781315366319-4, (77-106), (2017).
- Jianming Yang, Zhengfeng Li, Lizhong Guo, Juan Du and Hyeun-Jong Bae, Biosynthesis of β-caryophyllene, a novel terpene-based high-density biofuel precursor, using engineered Escherichia coli, Renewable Energy, 10.1016/j.renene.2016.06.061, 99, (216-223), (2016).
- Nimish Stephen, R Gayathri, R Niranjana, Yogendra K, Amit Das, Baskaran V and Ganesan P, Chapter 3 Carotenoids: Types, Sources, and Biosynthesis, Plant Secondary Metabolites, 3 Volume Set, 10.1201/9781315207506-14, (77-106), (2017).
- Fumiya Kurosaki, Takahiro Kato, Norihiko Misawa and Futoshi Taura, Efficient Production of δ-Guaiene, an Aroma Sesquiterpene Compound Accumulated in Agarwood, by Mevalonate Pathway-Engineered <i>Escherichia coli</i> Cells, Advances in Bioscience and Biotechnology, 07, 11, (435), (2016).
- Christoph Albermann and Holger Beuttler, Synthesis of β‐Carotene and Other Important Carotenoids with Bacteria, Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants, (227-263), (2016).
- Y. Li and G. Wang, Strategies of isoprenoids production in engineered bacteria, Journal of Applied Microbiology, 121, 4, (932-940), (2016).
- Lijun Ye, Chunzhi Zhang, Changhao Bi, Qingyan Li and Xueli Zhang, Combinatory optimization of chromosomal integrated mevalonate pathway for β-carotene production in Escherichia coli, Microbial Cell Factories, 10.1186/s12934-016-0607-3, 15, 1, (2016).
- Hong-Jie Shen, Bi-Yan Cheng, Yan-Mei Zhang, Liang Tang, Zhen Li, Yi-Fan Bu, Xi-Ran Li, Gui-Qiao Tian and Jian-Zhong Liu, Dynamic control of the mevalonate pathway expression for improved zeaxanthin production in Escherichia coli and comparative proteome analysis, Metabolic Engineering, 10.1016/j.ymben.2016.07.012, 38, (180-190), (2016).
- Jianming Yang and Qingjuan Nie, Engineering Escherichia coli to convert acetic acid to β-caryophyllene, Microbial Cell Factories, 15, 1, (2016).
- Hui Wu, Leepika Tuli, George N. Bennett and Ka-Yiu San, Metabolic transistor strategy for controlling electron transfer chain activity in Escherichia coli, Metabolic Engineering, 28, (159), (2015).
- Biqiang Chen, Yifeng Tao, Meng Wang, Di Cai and Tianwei Tan, Bioconversion of Biomass to Bulk Chemicals, Sustainable Production of Bulk Chemicals, 10.1007/978-94-017-7475-8_3, (51-68), (2015).
- Wenping Xie, Xiaomei Lv, Lidan Ye, Pingping Zhou and Hongwei Yu, Construction of lycopene-overproducing Saccharomyces cerevisiae by combining directed evolution and metabolic engineering, Metabolic Engineering, 10.1016/j.ymben.2015.04.009, 30, (69-78), (2015).
- Akinori Katabami, Ling Li, Miki Iwasaki, Maiko Furubayashi, Kyoichi Saito and Daisuke Umeno, Production of squalene by squalene synthases and their truncated mutants in Escherichia coli, Journal of Bioscience and Bioengineering, 119, 2, (165), (2015).
- Fiona K. Davies, Robert E. Jinkerson and Matthew C. Posewitz, Toward a photosynthetic microbial platform for terpenoid engineering, Photosynthesis Research, 10.1007/s11120-014-9979-6, 123, 3, (265-284), (2014).
- Cinzia Formighieri and Anastasios Melis, Carbon partitioning to the terpenoid biosynthetic pathway enables heterologous β-phellandrene production in Escherichia coli cultures, Archives of Microbiology, 10.1007/s00203-014-1024-9, 196, 12, (853-861), (2014).
- Fiona K. Bentley, Andreas Zurbriggen and Anastasios Melis, Heterologous Expression of the Mevalonic Acid Pathway in Cyanobacteria Enhances Endogenous Carbon Partitioning to Isoprene, Molecular Plant, 10.1093/mp/sst134, 7, 1, (71-86), (2014).
- Matthew C Posewitz, Engineering pathways to biofuels in photoautotrophic microorganisms, Biofuels, 10.4155/bfs.13.67, 5, 1, (67-78), (2014).
- CLAUDIA E. VICKERS, MAREIKE BONGERS, QING LIU, THIERRY DELATTE and HARRO BOUWMEESTER, Metabolic engineering of volatile isoprenoids in plants and microbes, Plant, Cell & Environment, 37, 8, (1753-1775), (2014).
- Christopher J. Tervo and Jennifer L. Reed, Expanding metabolic engineering algorithms using feasible space and shadow price constraint modules, Metabolic Engineering Communications, 1, (1), (2014).
- Xianzhong Chen, Li Zhou, Kangming Tian, Ashwani Kumar, Suren Singh, Bernard A. Prior and Zhengxiang Wang, Metabolic engineering of Escherichia coli: A sustainable industrial platform for bio-based chemical production, Biotechnology Advances, 10.1016/j.biotechadv.2013.02.009, 31, 8, (1200-1223), (2013).
- Yan Zhou, Komi Nambou, Liujing Wei, Jingjing Cao, Tadayuki Imanaka and Qiang Hua, Lycopene production in recombinant strains of Escherichia coli is improved by knockout of the central carbon metabolism gene coding for glucose-6-phosphate dehydrogenase, Biotechnology Letters, 10.1007/s10529-013-1317-0, 35, 12, (2137-2145), (2013).
- Brett A. Boghigian, Daniel Salas, Parayil Kumaran Ajikumar, Gregory Stephanopoulos and Blaine A. Pfeifer, Analysis of heterologous taxadiene production in K- and B-derived Escherichia coli, Applied Microbiology and Biotechnology, 10.1007/s00253-011-3528-4, 93, 4, (1651-1661), (2011).
- Sara Abolhassani Rad, Hossein Shahbani Zahiri, Kambiz Akbari Noghabi, Sarah Rajaei, Reza Heidari and Leila Mojallali, Type 2 IDI performs better than type 1 for improving lycopene production in metabolically engineered E. coli strains, World Journal of Microbiology and Biotechnology, 10.1007/s11274-011-0821-4, 28, 1, (313-321), (2011).
- Andreas Zurbriggen, Henning Kirst and Anastasios Melis, Isoprene Production Via the Mevalonic Acid Pathway in Escherichia coli (Bacteria), BioEnergy Research, 10.1007/s12155-012-9192-4, 5, 4, (814-828), (2012).
- Norihiko Misawa, Carotenoid β-Ring Hydroxylase and Ketolase from Marine Bacteria—Promiscuous Enzymes for Synthesizing Functional Xanthophylls, Marine Drugs, 9, 12, (757), (2011).
- Claudia Schmidt‐Dannert and Alexander Pisarchik, Biosynthetic Pathway Engineering Strategies, Protein Engineering Handbook, (849-876), (2011).
- Hui-Jeong Jang, Sang-Hwal Yoon, Hee-Kyung Ryu, Jung-Hun Kim, Chong-Long Wang, Jae-Yean Kim, Deok-Kun Oh and Seon-Won Kim, Retinoid production using metabolically engineered Escherichia coli with a two-phase culture system, Microbial Cell Factories, 10.1186/1475-2859-10-59, 10, 1, (59), (2011).
- Allison P. Heath, George N. Bennett and Lydia E. Kavraki, An Algorithm for Efficient Identification of Branched Metabolic Pathways, Journal of Computational Biology, 18, 11, (1575), (2011).
- Norihiko Misawa, Carotenoids, Comprehensive Natural Products II, 10.1016/B978-008045382-8.00009-5, (733-753), (2010).
- Sung-Woo Kim, Jae-Bum Kim, Ji-Myung Ryu, Joon-Ki Jung and Jung-Hoe Kim, High-level production of lycopene in metabolically engineered E. coli, Process Biochemistry, 10.1016/j.procbio.2009.04.018, 44, 8, (899-905), (2009).
- Sang-Hwal Yoon, Sook-Hee Lee, Amitabha Das, Hee-Kyoung Ryu, Hee-Jeong Jang, Jae-Yean Kim, Deok-Kun Oh, Jay D. Keasling and Seon-Won Kim, Combinatorial expression of bacterial whole mevalonate pathway for the production of β-carotene in E. coli, Journal of Biotechnology, 10.1016/j.jbiotec.2009.01.008, 140, 3-4, (218-226), (2009).
- Hisashi Harada, Fengnian Yu, Sho Okamoto, Tomohisa Kuzuyama, Ryutaro Utsumi and Norihiko Misawa, Efficient synthesis of functional isoprenoids from acetoacetate through metabolic pathway-engineered Escherichia coli, Applied Microbiology and Biotechnology, 81, 5, (915), (2009).
- Jung Hun Kim, Seon-Won Kim, Do Quynh Anh Nguyen, He Li, Sung Bae Kim, Yang-Gon Seo, Jae-Kyung Yang, In-Young Chung, Dae Hwan Kim and Chang-Joon Kim, Production of β-carotene by recombinant Escherichia coli with engineered whole mevalonate pathway in batch and fed-batch cultures, Biotechnology and Bioprocess Engineering, 14, 5, (559), (2009).
- Hisashi Harada and Norihiko Misawa, Novel approaches and achievements in biosynthesis of functional isoprenoids in Escherichia coli, Applied Microbiology and Biotechnology, 84, 6, (1021), (2009).
- Claudia Schmidt‐Dannert and Pyung Cheon Lee, Carotenoids, Microbial Processes, Encyclopedia of Industrial Biotechnology, (1-18), (2009).
- J.L. Fortman, Swapnil Chhabra, Aindrila Mukhopadhyay, Howard Chou, Taek Soon Lee, Eric Steen and Jay D. Keasling, Biofuel alternatives to ethanol: pumping the microbial well, Trends in Biotechnology, 10.1016/j.tibtech.2008.03.008, 26, 7, (375-381), (2008).
- Hal Alper and Gregory Stephanopoulos, Uncovering the gene knockout landscape for improved lycopene production in E. coli, Applied Microbiology and Biotechnology, 78, 5, (801), (2008).
- Irene Martínez, Jiangfeng Zhu, Henry Lin, George N. Bennett and Ka-Yiu San, Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways, Metabolic Engineering, 10.1016/j.ymben.2008.09.001, 10, 6, (352-359), (2008).
- Daniel Klein-Marcuschamer, Parayil Kumaran Ajikumar and Gregory Stephanopoulos, Engineering microbial cell factories for biosynthesis of isoprenoid molecules: beyond lycopene, Trends in Biotechnology, 25, 9, (417), (2007).
- Sang-Hwal Yoon, Ju-Eun Kim, Sook-Hee Lee, Hye-Min Park, Myung-Suk Choi, Jae-Yean Kim, Si-Hyoung Lee, Yong-Chul Shin, Jay D. Keasling and Seon-Won Kim, Engineering the lycopene synthetic pathway in E. coli by comparison of the carotenoid genes of Pantoea agglomerans and Pantoea ananatis, Applied Microbiology and Biotechnology, 10.1007/s00253-006-0623-z, 74, 1, (131-139), (2006).
- Amitabha Das, Sang-Hwal Yoon, Sook-Hee Lee, Jae-Yean Kim, Deok-Kun Oh and Seon-Won Kim, An update on microbial carotenoid production: application of recent metabolic engineering tools, Applied Microbiology and Biotechnology, 10.1007/s00253-007-1206-3, 77, 3, (505-512), (2007).
- Sang‐Hwal Yoon, Hye‐Min Park, Ju‐Eun Kim, Sook‐Hee Lee, Myung‐Suk Choi, Jae‐Yean Kim, Deok‐Kun Oh, Jay D. Keasling and Seon‐Won Kim, Increased β‐Carotene Production in Recombinant Escherichia coli Harboring an Engineered Isoprenoid Precursor Pathway with Mevalonate Addition, Biotechnology Progress, 23, 3, (599-605), (2008).
- Francis X. Cunningham and Elisabeth Gantt, A portfolio of plasmids for identification and analysis of carotenoid pathway enzymes: Adonis aestivalis as a case study, Photosynthesis Research, 10.1007/s11120-007-9210-0, 92, 2, (245-259), (2007).
- Sang-Hwal Yoon, Young-Mi Lee, Ju-Eun Kim, Sook-Hee Lee, Joo-Hee Lee, Jae-Yean Kim, Kyung-Hwa Jung, Yong-Chul Shin, Jay D. Keasling and Seon-Won Kim, Enhanced lycopene production inEscherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from mevalonate, Biotechnology and Bioengineering, 94, 6, (1025), (2006).
- Xiulai Chen, Cong Gao, Liang Guo, Guipeng Hu, Qiuling Luo, Jia Liu, Jens Nielsen, Jian Chen and Liming Liu, DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals, Chemical Reviews, 10.1021/acs.chemrev.6b00804, (2017).




