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Single-Stage Astaxanthin Production Enhances the Nonmevalonate Pathway and Photosynthetic Central Metabolism in Synechococcus sp. PCC 7002
journal contribution
posted on 2019-11-08, 20:34 authored by Tomohisa Hasunuma, Ayako Takaki, Mami Matsuda, Yuichi Kato, Christopher J. Vavricka, Akihiko KondoThe
natural pigment astaxanthin is widely used in aquaculture,
pharmaceutical, nutraceutical, and cosmetic industries due to superior
antioxidant properties. The green alga Haematococcus pluvialis is currently used for commercial production of astaxanthin pigment.
However, slow growing H. pluvialis requires
a complex two-stage stress-induced process with high light intensity
leading to increased contamination risks. In contrast, the fast-growing
euryhaline cyanobacterium Synechococcus sp. PCC 7002
(Synechococcus 7002) is able to reach high density
under stress-free phototrophic conditions, and is therefore a promising
metabolic engineering platform for astaxanthin production. In the
present study, genes encoding β-carotene hydroxylase and β-carotene
ketolase, from the marine bacterium Brevundimonas sp. SD212, are integrated into the endogenous plasmid of Synechococcus 7002, and then expressed to biosynthesize
astaxanthin. Although Synechococcus 7002 does not
inherently produce astaxanthin, the recombinant ZW strain yields 3
mg/g dry cell weight astaxanthin from CO2 as the sole carbon
source, with significantly higher astaxanthin content than previous
cyanobacteria reports. Synechococcus 7002 astaxanthin
productivity reached 3.35 mg/L/day after just 2 days in a continuous
autotrophic process, which is comparable to the best H. pluvialis astaxanthin productivities when factoring in growth times. Metabolomics
analysis reveals increases in fractions of hexose-, pentose-, and
triose phosphates along with intermediates involved in the nonmevalonate
pathway. Dynamic metabolomics analysis of 13C labeled metabolites
clearly indicates flux enhancements in the Calvin cycle and glycolysis
resulting from the overexpression of astaxanthin biosynthetic genes.
This study suggests that cyanobacteria may enhance central metabolism
as well as the nonmevalonate pathway in an attempt to replenish depleted
pigments such as β-carotene and zeaxanthin.
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astaxanthin biosynthetic geneseuryhaline cyanobacterium Synechococcus spSingle-Stage Astaxanthin Production Enhancescell weight astaxanthinalga Haematococcus pluvialis. pluvialiH . pluvialis astaxanthin productivitiesPCC 7002ZWtwo-stage stress-induced processSynechococcus 7002 astaxanthin productivitygenes encoding β- carotene hydroxylaseβ- carotene ketolasemarine bacterium Brevundimonas spnonmevalonate pathwayCOH . pluvialisSDDynamic metabolomics analysisPhotosynthetic Central Metabolismstress-free phototrophic conditions
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