Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria

Choi, Sun Young; Lee, Hyun Jeong; Choi, Jaeyeon; Kim, Jiye; Sim, Sang Jun; Um, Youngsoon; Kim, Yunje; Lee, Taek Soon; Keasling, Jay D.; Woo, Han Min

doi:10.1186/s13068-016-0617-8

Title: Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria

Journal Article · 22 September 2016 · Biotechnology for Biofuels

DOI: https://doi.org/10.1186/s13068-016-0617-8 · OSTI ID:1626977

Choi, Sun Young ^[1]; Lee, Hyun Jeong ^[2]; Choi, Jaeyeon ^[2]; Kim, Jiye ^[3]; Sim, Sang Jun ^[4]; Um, Youngsoon ^[2]; Kim, Yunje ^[2]; Lee, Taek Soon ^[5]; Keasling, Jay D. ^[6];

^[7]

Korea Inst. of Science and Technology, Seoul (Korea, Republic of). Clean Energy Research Center; Korea Univ., Seoul (Korea, Republic of). Green School. Graduate school of Energy and Environment; DOE/OSTI
Korea Inst. of Science and Technology, Seoul (Korea, Republic of). Clean Energy Research Center
Korea Inst. of Science and Technology, Seoul (Korea, Republic of). Clean Energy Research Center; Korea Univ., Seoul (Korea, Republic of). Dept. of Chemistry
Korea Univ., Seoul (Korea, Republic of). Green School. Graduate school of Energy and Environment; Korea Univ., Seoul (Korea, Republic of). Dept. of Chemical and Biological Engineering
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering; Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering
Sungkyunkwan Univ., Suwon (Republic of Korea). Dept. of Food Science and Biotechnology

Background: Metabolic engineering of cyanobacteria has enabled photosynthetic conversion of CO2 to value added chemicals as bio-solar cell factories. However, the production levels of isoprenoids in engineered cyanobacteria were quite low, compared to other microbial hosts. Therefore, modular optimization of multiple gene expressions for metabolic engineering of cyanobacteria is required for the production of farnesyl diphosphate-derived isoprenoids from CO2. Results: Here, we engineered Synechococcus elongatus PCC 7942 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and the amorphadiene synthase for production of amorpha-4,11-diene, resulting in significantly increased levels (23-fold) of amorpha-4,11-diene (19.8 mg/L) in the best strain relative to a parental strain. Replacing amorphadiene synthase with squalene synthase led to the synthesis of a high amount of squalene (4.98 mg/L/OD730). Overexpression of farnesyl diphosphate synthase is the most critical factor for the significant production, whereas overexpression of 1-deoxy-d-xylulose 5-phosphate reductase is detrimental to the cell growth and the production. Additionally, the cyanobacterial growth inhibition was alleviated by expressing a terpene synthase in S. elongatus PCC 7942 strain with the optimized MEP pathway only (SeHL33). Conclusions: This is the first demonstration of photosynthetic production of amorpha-4,11-diene from CO2 in cyanobacteria and production of squalene in S. elongatus PCC 7942. Our optimized modular Over MEP strain (SeHL33) with either co-expression of ADS or SQS demonstrated the highest production levels of amorpha-4,11-diene and squalene, which could expand the list of farnesyl diphosphate-derived isoprenoids from CO2 as bio-solar cell factories.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1626977

Journal Information:: Biotechnology for Biofuels, Journal Name: Biotechnology for Biofuels Journal Issue: 1 Vol. 9; ISSN 1754-6834

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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Heterologous Expression of the Mevalonic Acid Pathway in Cyanobacteria Enhances Endogenous Carbon Partitioning to Isoprene Bentley, Fiona K.; Zurbriggen, Andreas; Melis, Anastasios Molecular Plant, Vol. 7, Issue 1 https://doi.org/10.1093/mp/sst134	journal	January 2014
Translation rate is controlled by coupled trade-offs between site accessibility, selective RNA unfolding and sliding at upstream standby sites Espah Borujeni, Amin; Channarasappa, Anirudh S.; Salis, Howard M. Nucleic Acids Research, Vol. 42, Issue 4 https://doi.org/10.1093/nar/gkt1139	journal	November 2013
Overexpression of the lemon basil α-zingiberene synthase gene increases both mono- and sesquiterpene contents in tomato fruit: Overexpression of ZIS in tomato fruit Davidovich-Rikanati, Rachel; Lewinsohn, Efraim; Bar, Einat The Plant Journal, Vol. 56, Issue 2 https://doi.org/10.1111/j.1365-313X.2008.03599.x	journal	July 2008
Engineering of a modular and synthetic phosphoketolase pathway for photosynthetic production of acetone from CO ₂ in S ynechococcus elongatus PCC 7942 under light and aerobic condition Chwa, Jun‐Won; Kim, Wook Jin; Sim, Sang Jun Plant Biotechnology Journal, Vol. 14, Issue 8 https://doi.org/10.1111/pbi.12536	journal	February 2016
In Silico Identification of Gene Amplification Targets for Improvement of Lycopene Production Choi, H. S.; Lee, S. Y.; Kim, T. Y. Applied and Environmental Microbiology, Vol. 76, Issue 10 https://doi.org/10.1128/AEM.00115-10	journal	March 2010
Identification of Sesquiterpene Synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. Strain PCC 7120 Agger, Sean A.; Lopez-Gallego, Fernando; Hoye, Thomas R. Journal of Bacteriology, Vol. 190, Issue 18 https://doi.org/10.1128/JB.00759-08	journal	July 2008
Biosynthesis of Plant Isoprenoids: Perspectives for Microbial Engineering Kirby, James; Keasling, Jay D. Annual Review of Plant Biology, Vol. 60, Issue 1 https://doi.org/10.1146/annurev.arplant.043008.091955	journal	June 2009
BglBrick vectors and datasheets: A synthetic biology platform for gene expression Lee, Taek; Krupa, Rachel A.; Zhang, Fuzhong Journal of Biological Engineering, Vol. 5, Issue 1 https://doi.org/10.1186/1754-1611-5-12	journal	January 2011
Production of Squalene in Synechocystis sp. PCC 6803 Englund, Elias; Pattanaik, Bagmi; Ubhayasekera, Sarojini Jayantha K. PLoS ONE, Vol. 9, Issue 3 https://doi.org/10.1371/journal.pone.0090270	journal	March 2014
Engineering Limonene and Bisabolene Production in Wild Type and a Glycogen-Deficient Mutant of Synechococcus sp. PCC 7002 Davies, Fiona K.; Work, Victoria H.; Beliaev, Alexander S. Frontiers in Bioengineering and Biotechnology, Vol. 2 https://doi.org/10.3389/fbioe.2014.00021	journal	June 2014

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biotechnology & Applied Microbiology
Cyanobacteria
Energy & Fuels
Isoprenoids
Metabolic engineering
Synthetic biology

Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria Choi, Sun; Lee, Hyun; Choi, Jaeyeon https://doi.org/10.6084/m9.figshare.c.3625784 The current record is supplemented by this collection	collection	January 2016
Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria Choi, Sun; Lee, Hyun; Choi, Jaeyeon https://doi.org/10.6084/m9.figshare.c.3625784.v1 The current record is supplemented by this collection	collection	January 2016
MOESM1 of Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria Choi, Sun; Lee, Hyun; Choi, Jaeyeon https://doi.org/10.6084/m9.figshare.c.3625784_d1 The current record is supplemented by this text	text	January 2016
MOESM1 of Photosynthetic conversion of CO2 to farnesyl diphosphate-derived phytochemicals (amorpha-4,11-diene and squalene) by engineered cyanobacteria Choi, Sun; Lee, Hyun; Choi, Jaeyeon https://doi.org/10.6084/m9.figshare.c.3625784_d1.v1 The current record is supplemented by this text	text	January 2016