The 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.

中文翻译：

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单阶段虾青素的生产增强了Synechococcus sp。中的非甲羟戊酸途径和光合中央代谢。PCC 7002。

天然色素虾青素由于具有出色的抗氧化性能，被广泛用于水产养殖，制药，营养保健品和化妆品行业。绿藻类雨生红球菌目前被用于商业生产虾青素色素。但是，生长缓慢的幽门螺杆菌需要一个复杂的两阶段应力诱导过程，并具有较高的光强度，这会增加污染的风险。相比之下，快速增长的euryhaline蓝细菌Synechococcus sp。PCC 7002（Synechococcus 7002）能够在无胁迫的光养条件下达到高密度，因此是生产虾青素的有前途的代谢工程平台。在本研究中，来自海洋细菌Brevundimonas sp。的编码β-胡萝卜素羟化酶和β-胡萝卜素酮醇酶的基因。SD212，将其整合到Syechococcus 7002的内源质粒中，然后表达以生物合成虾青素。尽管Synechococcus 7002并非固有地产生虾青素，但重组ZW菌株从作为唯一碳源的CO2中产生3 mg / g干细胞重量的虾青素，其虾青素含量明显高于以前的蓝细菌报告。在连续的自养过程中，仅持续两天，Synechococcus 7002虾青素的生产率就达到了3.35 mg / L /天，这在考虑生长时间时可与最佳的幽门螺杆菌虾青素生产率相媲美。代谢组学分析显示，己糖，戊糖和三糖磷酸酯以及与非甲羟戊酸途径有关的中间体的比例增加。对13C标记代谢物的动态代谢组学分析清楚地表明，虾青素生物合成基因的过表达会导致Calvin循环和糖酵解的通量增强。这项研究表明，蓝细菌可能会增强中枢代谢以及非甲羟戊酸途径，从而尝试补充枯竭的色素（例如β-胡萝卜素和玉米黄质）。