Table 1.
Summary of recent advances in metabolic engineering of cyanobacteria for terpenoids production
| Pathway engineered | Host strain | Terpenoid synthesized | Characteristic(s) of modified strain | Maximum yield | References | |
|---|---|---|---|---|---|---|
| mg/L | mg/g DCW | |||||
| Upstream MEP and downstream | UTEX 2973 | Limonene | Single nucleotide mutated GPPS gene, with co-expressed lims, DXS, and IDI | 16.4a | – | Lin et al. (2021) |
| PCC 6803 | Bisabolene | Expresses CfDXS, sIDI; AgB, EcFPPS |
9b 200c |
17b – |
Rodrigues and Lindberg (2021) | |
| Squalene | shc gene inactivated by replacing with BSS. Also expresses CfDXS, IDI, and EcFPPS | 5.1d | – | Pattanaik et al. (2020) | ||
| Astaxanthin | Expresses CrtZ and CrtW with DXS | 1.089a | – | Shimada et al. (2020) | ||
| Isoprene | Expresses IDI, DXS, and EgIspS | 1.0e | 2.8e | Englund et al. (2018) | ||
| Expresses fni, and IspS fused with cpcB | – | 12.3f | Chaves and Melis (2018) | |||
| β-Phellandrene | Expresses GPPS and PHLS | – | 24.0f | Betterle and Melis (2019) | ||
| Geranyllinalool | Expresses NaGLS | – | 0.36a | Formighieri and Melis (2017) | ||
| Lycopene | Expresses DXS, GGPPS, Crtb, and CrtI | 6 g | 1.48g | Taylor et al. (2021) | ||
| PCC 7942 | Farnesene | Expresses DXS, IDI, EcFPPS, and AFS, while replacing ccm gene cluster with bicA and CA gene | 5.0 h | – | Lee et al. (2021) | |
| Farnesene | Expresses RBS optimized AFS with DXS, IDI, and EcFPPS | 5.66a | – | Pattharaprachayakul et al. (2019) | ||
| Farnesene | Co-expression of DXS, IDI and EcFPPS with AFS | 4.6 h | – | Lee et al. (2017) | ||
| Squalene | Expresses DXS, IDI, EcFPPS and SQS | 4.98a | – | Choi et al. (2016) | ||
| Amorphadiene | Expresses DXS, IDI, EcFPPS and ADS under trc promoter | 19.8a | – | Choi et al. (2016) | ||
| Downstream | PCC 6803 | Bisabolene | Optimized RBS for AgB and EcFPPS | 22.2a | – | Sebesta and Peebles (2020) |
| Expresses AgB under PetE promoter | 179.4i | – | Dienst et al. (2020) | |||
| Valencene | Expressed CnValCS and EcFPPS | 9.62a | 2.88a | Matsudaira et al. (2020) | ||
| Manoyl oxide | Expresses CfTPS2 and CfTPS3 | 2j | – | Vavitsas et al. (2017) | ||
| PCC 7002 | Astaxanthin | Expresses CrtZ and CrtW under psbA2 promoter | 3.35a | 3.0a | Hasunuma et al. (2019) | |
| Upstream MEP, downstream, PHB and glycolate synthesis | PCC 6803 | Isoprene | Expresses IspS gene in place of pta gene; DXS, IDI, IspD, IspE in place of phaCE gene; deleted glcD1 and glcD2 gene | 0.084a | – | Zhou et al. (2021) |
| Downstream and PPP | PCC 6803 | Limonene | Expresses rpi, rpe gene with GPPS and lims | 6.7a | – | Lin et al. 2017 |
Strains PCC 6803: Synechocystis sp. PCC 6803; PCC 7942: Synechococcus elongatus PCC 7942; UTEX 2973: Synechococcus elongatus UTEX 2973; PCC 7002: Synechococcus sp. PCC 7002
DCW dry cell weight, GPPS geranylgeranyl diphosphate synthase, lims limonene synthase from Mentha piperita, EgIspS isoprene synthase from Eucalyptus globulus, cfDXS DXP synthase, from Coleus forskohlii, sIDI IPP/DMAPP isomerase from Synechocystis sp. PCC 6803, AgB bisabolene synthase from Abies grandies, fni IDI from Streptococcus pneumoniae, cpcB β-subunit of phycocyanin, PHLS β-Phellandrene synthase, NaGLS geranyllinalool synthase from Nicotiana attenuate, DXS DXP synthase, GGPPS GGPP synthase, CrtB phytoene synthase, CrtI phytoene desaturase, EcFPPS FPP synthase from Escherichia coli, BSS squalene synthase from Botryococcus braunii, shc squalene hopase cyclase, CnValCS valencene synthase from Callitropsis nootkatensis, CfTPS2 diterpene synthase TPS2 from Plectranthus barbatus, CfTPS3 diterpene synthase TPS3 from Plectranthus barbatus, rpi ribose 5-phosphate isomerase, rpe ribulose 5-phosphate 3-epimerase, RBS ribosome binding site, AFS farnesene synthase gene from Malus domestica, CrtZ β-carotene hydroxylase from Brevundimonas sp. SD212, CrtW β-carotene ketolase from Brevundimonas sp. SD212, ADS amorphadiene synthase from Artemisia annua, SQS squalene synthase from Saccharomyces cerevisiae, ccm β-carboxysome, bicA bicarbonate transporter of PCC 6803, CA carbonic anhydrase, pta phosphotransacetylase, IspD 2-C-methyld-erythritol 4-phosphate cytidyltransferase, IspE 4-diphosphocytidyl-2-Cmethyl-d-erythritol kinase, phaCE polyhydroxybutyrate (PHB) synthesis, glcD1 and glcD2 glycolate dehydrogenase, PPP Pentose phosphate pathway
Culture conditions ashake flask; bMC1000 multicultivator system; chigh-density cultivation system; dflat panel bioreactor; escrew cap bottles; fone-liter fed-batch bioreactor; g25-ml vented culture flask; h100-ml duran bottle; ihigh-density cultivation system in two-step semi-batch mode; j50-ml glass tube