Metabolic Engineering of Escherichia Coli for Producing Astaxanthin As the Predominant Carotenoid

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2017 Sep 23

PMID 28937591

Citations 19

Authors

Qian Lu

Yi-Fan Bu

Jian-Zhong Liu

Affiliations

Soon will be listed here.

Abstract

Astaxanthin is a carotenoid of significant commercial value due to its superior antioxidant potential and wide applications in the aquaculture, food, cosmetic and pharmaceutical industries. A higher ratio of astaxanthin to the total carotenoids is required for efficient astaxanthin production. β-Carotene ketolase and hydroxylase play important roles in astaxanthin production. We first compared the conversion efficiency to astaxanthin in several β-carotene ketolases from sp. SD212, sp. DC18, sp. PC1, sp. N81106 and with the recombinant cells that synthesize zeaxanthin due to the presence of the The sp. SD212 and genes are the best combination for astaxanthin production. After balancing the activities of β-carotene ketolase and hydroxylase, an ASTA-1 that carries neither a plasmid nor an antibiotic marker was constructed to produce astaxanthin as the predominant carotenoid (96.6%) with a specific content of 7.4 ± 0.3 mg/g DCW without an addition of inducer.

Citing Articles

Biotechnological advances for improving natural pigment production: a state-of-the-art review.

Lyu X, Lyu Y, Yu H, Chen W, Ye L, Yang R Bioresour Bioprocess. 2024; 9(1):8.

PMID: 38647847 PMC: 10992905. DOI: 10.1186/s40643-022-00497-4.

Enhancing astaxanthin biosynthesis and pathway expansion towards glycosylated C40 carotenoids by Corynebacterium glutamicum.

Gottl V, Meyer F, Schmitt I, Persicke M, Peters-Wendisch P, Wendisch V Sci Rep. 2024; 14(1):8081.

PMID: 38582923 PMC: 10998873. DOI: 10.1038/s41598-024-58700-9.

Production of Astaxanthin Using CBFD1/HFBD1 from and the Isopentenol Utilization Pathway in .

Roth J, Ward V Bioengineering (Basel). 2023; 10(9).

PMID: 37760135 PMC: 10525928. DOI: 10.3390/bioengineering10091033.

Metabolic Engineering of Model Microorganisms for the Production of Xanthophyll.

Wang N, Peng H, Yang C, Guo W, Wang M, Li G Microorganisms. 2023; 11(5).

PMID: 37317226 PMC: 10223009. DOI: 10.3390/microorganisms11051252.

Overlapping promoter library designed for rational heterogenous expression in Cordyceps militaris.

Lyu M, Zeng J, Zhou Y, Zhang T, Wang A, Ma J Microb Cell Fact. 2022; 21(1):107.

PMID: 35655187 PMC: 9161592. DOI: 10.1186/s12934-022-01826-0.

References

Fraser P, Miura Y, Misawa N . In vitro characterization of astaxanthin biosynthetic enzymes. J Biol Chem. 1997; 272(10):6128-35. DOI: 10.1074/jbc.272.10.6128. View

Ye R, Stead K, Yao H, He H . Mutational and functional analysis of the beta-carotene ketolase involved in the production of canthaxanthin and astaxanthin. Appl Environ Microbiol. 2006; 72(9):5829-37. PMC: 1563626. DOI: 10.1128/AEM.00918-06. View

Henke N, Heider S, Peters-Wendisch P, Wendisch V . Production of the Marine Carotenoid Astaxanthin by Metabolically Engineered Corynebacterium glutamicum. Mar Drugs. 2016; 14(7). PMC: 4962014. DOI: 10.3390/md14070124. View

Misawa N . Carotenoid β-ring hydroxylase and ketolase from marine bacteria-promiscuous enzymes for synthesizing functional xanthophylls. Mar Drugs. 2011; 9(5):757-771. PMC: 3111180. DOI: 10.3390/md9050757. View

Makino T, Harada H, Ikenaga H, Matsuda S, Takaichi S, Shindo K . Characterization of cyanobacterial carotenoid ketolase CrtW and hydroxylase CrtR by complementation analysis in Escherichia coli. Plant Cell Physiol. 2008; 49(12):1867-78. DOI: 10.1093/pcp/pcn169. View

Scaife M, Ma C, Ninlayarn T, Wright P, Armenta R . Comparative analysis of β-carotene hydroxylase genes for astaxanthin biosynthesis. J Nat Prod. 2012; 75(6):1117-24. DOI: 10.1021/np300136t. View

Lee P, Schmidt-Dannert C . Metabolic engineering towards biotechnological production of carotenoids in microorganisms. Appl Microbiol Biotechnol. 2002; 60(1-2):1-11. DOI: 10.1007/s00253-002-1101-x. View

Li X, Tian G, Shen H, Liu J . Metabolic engineering of Escherichia coli to produce zeaxanthin. J Ind Microbiol Biotechnol. 2014; 42(4):627-36. DOI: 10.1007/s10295-014-1565-6. View

Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H . Astaxanthin, a carotenoid with potential in human health and nutrition. J Nat Prod. 2006; 69(3):443-9. DOI: 10.1021/np050354+. View

10.

Boel G, Letso R, Neely H, Price W, Wong K, Su M . Codon influence on protein expression in E. coli correlates with mRNA levels. Nature. 2016; 529(7586):358-363. PMC: 5054687. DOI: 10.1038/nature16509. View

11.

Lemuth K, Steuer K, Albermann C . Engineering of a plasmid-free Escherichia coli strain for improved in vivo biosynthesis of astaxanthin. Microb Cell Fact. 2011; 10:29. PMC: 3111352. DOI: 10.1186/1475-2859-10-29. View

12.

Choi S, Harada H, Matsuda S, Misawa N . Characterization of two beta-carotene ketolases, CrtO and CrtW, by complementation analysis in Escherichia coli. Appl Microbiol Biotechnol. 2007; 75(6):1335-41. DOI: 10.1007/s00253-007-0967-z. View

13.

Choi S, Nishida Y, Matsuda S, Adachi K, Kasai H, Peng X . Characterization of beta-carotene ketolases, CrtW, from marine bacteria by complementation analysis in Escherichia coli. Mar Biotechnol (NY). 2005; 7(5):515-22. DOI: 10.1007/s10126-004-5100-z. View

14.

Fraser P, Shimada H, Misawa N . Enzymic confirmation of reactions involved in routes to astaxanthin formation, elucidated using a direct substrate in vitro assay. Eur J Biochem. 1998; 252(2):229-36. DOI: 10.1046/j.1432-1327.1998.2520229.x. View

15.

Zhou P, Ye L, Xie W, Lv X, Yu H . Highly efficient biosynthesis of astaxanthin in Saccharomyces cerevisiae by integration and tuning of algal crtZ and bkt. Appl Microbiol Biotechnol. 2015; 99(20):8419-28. DOI: 10.1007/s00253-015-6791-y. View

16.

Ye V, Bhatia S . Pathway engineering strategies for production of beneficial carotenoids in microbial hosts. Biotechnol Lett. 2012; 34(8):1405-14. DOI: 10.1007/s10529-012-0921-8. View

17.

Martin J, Gudina E, Barredo J . Conversion of beta-carotene into astaxanthin: Two separate enzymes or a bifunctional hydroxylase-ketolase protein?. Microb Cell Fact. 2008; 7:3. PMC: 2288588. DOI: 10.1186/1475-2859-7-3. View

18.

Zhong Y, Huang J, Liu J, Li Y, Jiang Y, Xu Z . Functional characterization of various algal carotenoid ketolases reveals that ketolating zeaxanthin efficiently is essential for high production of astaxanthin in transgenic Arabidopsis. J Exp Bot. 2011; 62(10):3659-69. PMC: 3130182. DOI: 10.1093/jxb/err070. View

19.

Zhou P, Xie W, Li A, Wang F, Yao Z, Bian Q . Alleviation of metabolic bottleneck by combinatorial engineering enhanced astaxanthin synthesis in Saccharomyces cerevisiae. Enzyme Microb Technol. 2017; 100:28-36. DOI: 10.1016/j.enzmictec.2017.02.006. View

20.

Guzman L, Belin D, CARSON M, Beckwith J . Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol. 1995; 177(14):4121-30. PMC: 177145. DOI: 10.1128/jb.177.14.4121-4130.1995. View