Table 2 Engineering microorganisms for astaxanthin production
From: Biotechnological advances for improving natural pigment production: a state-of-the-art review
Strain | Strategy | Cultivation mode | Astaxanthin yield | Refs. |
|---|---|---|---|---|
E. coli | Gene screening (four CrtZ and twelve CrtW genes) and gene combination | Shake flask | 1.99 mg/g DCW | Scaife et al. (2012) |
E. coli | Genomic integration (crtE, crtB, crtI, crtY and crtZ genes from P. ananatis as well as crtW148 gene from N. punctiforme PCC 73102) and promoter engineering | Shake flask | 1.4 mg/g DCW | Lemuth et al. (2011) |
E. coli | Optimization of gene expression via ribosome-binding site combinatorics | Shake flask | 5.8 mg/g DCW | Zelcbuch et al. (2013) |
E. coli | Gene mining of CrtE and CrtZ genes from Sphingomonas sp. ATCC 55669 | Shake flask | 6.6 mg/g DCW | Ma et al. (2016) |
E. coli | Combinatorial expression of different β-carotene ketolase and ketolases | Shake flask | 7.4 ± 0.3 mg/g DCW | Lu et al. (2017) |
E. coli | Pathway engineering- metabolic engineering of DXP pathway by introduction of genes from Kocuria gwangalliensis, as well as introduction of astaxanthin downstream biosynthetic pathway from Paracoccus haeundaensis | Shake flask | 1100 μg/g DCW | Jeong et al. (2018) |
E. coli | Optimization of gene codon, promoters, strain species and culture media | Shake flask | 4.30 ± 0.23 mg/g DCW 24.16 ± 2.03 mg/L | Li and Huang (2018) |
E. coli | Comprehensive metabolic engineering, consisting of optimization of β-carotene biosynthetic pathway, introduction of CrtZ from Pantoea ananatis and CrBKT from Chlamydomonas reinhardtii, truncation of CrBKT, culture condition optimization, strengthening of DXP pathway and uptake of glycerol, introduction of hok/sok system for improving the stability of hereditary stability | Fed-batch fermentation | 432.82 mg/L | Park et al. (2018) |
E. coli | Optimization of the localization of CrtZ and CrtW enzymes; a total of 215.4% improved production of astaxanthin was achieved by combining CrtZ and CrtW together with a linker and locating them on the cell membrane | Shake flask | No clear data | Ye et al. (2018) |
E. coli | Multidimensional heuristic process was proposed to optimization of the long astaxanthin biosynthetic pathway, via inter-module balance by varying promoter strength and intra-module balance by using different RBSs | Shake flask | 15.1 mg/g DCW 320 mg/L | Zhang et al. (2018b) |
E. coli | Optimization of gene expression by using different inducible and constitutive promoters | Shake flask | 8.3 mg/g DCW | Chou et al. (2019) |
E. coli | Optimization of cell morphology and oxidative stress for increasing astaxanthin yield, via gene mining and gene deletion. A complementary temperature-sensitive plasmid was introduced to further balance cell growth and production accumulation | Fed-batch fermentation | 432.82Â mg/L | Lu and Liu (2019) |
E. coli | Gene fusion of CrtW and CrtZ | Shake flask | 576.4 μg/g DCW | Nogueira et al. (2019) |
E. coli | Assembly of the key enzymes in the MVA pathway (ACAT, HMGS, HMGR) into multi-enzyme complexes via orthogonal protein reactions (SpyCatcher/SpyTag and SnoopCatcher/SnoopTag pairs) | Shake flask | 1 mg/g DCW | Qu et al. (2019) |
E. coli | Gene screening and enzyme fusion of CrtZ and CrtW, replacement of different linkers, carbon source optimization | Shake flask | 26.16 mg/L (5.18 mg/g DCW) | Wu et al. (2019b) |
E. coli | Coordinated expression of astaxanthin biosynthesis genes – CrtW, CrtZ, CrtY, and regulation of molecular chaperone genes groES-groEL in the beta-carotene producing strain CAR026 (3.6 g/L) | Fed-batch fermentation | 1.18 g/L | Gong et al. (2020) |
C. glutamicum | Balancing the metabolic flux of CrtZ and CrtW via selection and combination of different enzymes, optimization of RBS, and initiation codon | Shake flask | 0.4 mg·L−1·h−1 | Henke et al. (2016) |
C. glutamicum | Gene fusion of CrtZ and CrtW (CrtZ-CrtW help to accumulation astaxanthin while CrtZ-CrtW cannot produce astaxanthin); usage of combined carbon sources—glucose and acetic acid | Shake flask | 3.1 mg/g DCW | Henke and Wendisch (2019) |
C. utilis | Expression of CrtE, CrtB, CrtI, CrtY, CrtZ and CrtW genes with constitutive promoters | Shake flask | 0.4 mg/g DCW | Miura et al. (1998) |
Y. lipolytica | Introduction of CrtYB, CrtI, and CrtE gene from Phaffia rhodozyma, overexpression of endogenous tHMG1, multi-copy integration of CrtZ and CrtW gene into the genome, deregulation of ERG9 | 96-well plates | 3.5 mg/g DCW 54.6 mg/L | Kildegaard et al. (2017) |
Y. lipolytica | Optimization of the synthetic pathway of β-carotene precursor; optimization of the copy number as well as gene origins of β-ketolase and β-hydroxylase | Fed-batch fermentation | 285 ± 19 mg/L | Tramontin et al. (2019) |
K. marxianus | Gene screening of CrtZ and integration of astaxanthin biosynthetic pathway | Shake flask | No clear information | Chang et al. (2015) |
K. marxianus | Site mutation of CrtZ and overexpression of the key enzymes in the limiting steps | Batch fermentation | 9.972 mg/g DCW | Lin et al. (2017) |
S. cerevisiae | Overexpression of Crt genes from Phaffia rhodozyma or bacteria | Shake flask | 29 μg/g DCW | Ukibe et al. (2009) |
S. cerevisiae | Gene cloning, codon optimization and copy number optimization of CrtZ and BKT from H. pluvialis | Shake flask | 4.7 mg/g DCW | Zhou et al. (2015a) |
S. cerevisiae | Strengthening MVA pathway and β-carotene biosynthetic pathway, site-directed evolution of BKT, optimization of gene copy number, strain hybridization | Shake flask | 8.10 mg/g DCW 47.18 mg/L | Zhou et al. (2017a) |
S. cerevisiae | Combination of different CrtZ and CrtW genes from diverse origins, improvement of CrtZ promoter strength | Shake flask Fed-batch fermentation | 4.5 mg/g DCW 81.0 mg/L | Chen et al. (2017a) |
S. cerevisiae | Directed coevolution of β-carotene ketolase and hydroxylase, dynamic control of gene expression using temperature signal | Fed-batch fermentation | 235 mg/L | Zhou et al. (2019) |
S. cerevisiae | Introduction of CrtZ from Agrobacterium aurantiacum, atmospheric and room temperature plasma mutagenesis (ARTP) | Fed-batch fermentation | 217.9 mg/L | Jin et al. (2018) |
S. cerevisiae | Physical mutagenesis by ARTP and adaptive evolution driven by H2O2 | Fed-batch fermentation | 404.78Â mg/L | Jiang et al. (2020) |
S. cerevisiae | In vitro and in vivo recombination of diverse heterologous CrtZ and CrtW genes | Shake flask | 6.05 mg/g DCW | Qi et al. (2020) |