Engineering of the fast-growing cyanobacterium Synechococcus sp. PCC 11901 to synthesize astaxanthin

Astaxanthin is a red pigment required by feed, nutraceutical, and cosmetic industries for its pigmentation and antioxidant properties. This carotenoid is one of the main high-value products that can nowadays be derived from microalgae cultivation, raising important industrial interest. However, state-of-the-art astaxanthin production is the cultivation of the green alga Haematococcus pluvialis (or lacustris), which faces high costs and low production yield. Hence, alternative and efficient sources for astaxanthin need to be developed, and novel biotechnological solutions must be found. The recently discovered cyanobacterium, Synechococcus sp. PCC 11901 is a promising photosynthetic platform for the large-scale production of high-value products, but its potential has yet to be thoroughly tested.

In this study, the cyanobacterium Synechococcus sp. PCC 11901 was engineered for the first time to our knowledge to produce astaxanthin, a high-value ketocarotenoid, by expressing recombinant β-ketolase (bKT) and a β-hydroxylase enzymes (CtrZ). During photoautotrophic growth, the bKT-CtrZ transformed strain (called BC) accumulated astaxanthin to above 80% of the total carotenoid. Moreover, BC cells grew faster than wild-type (WT) cells in high light and continuous bubbling with CO₂-enriched air. The engineered strain reached stationary phase after only 4 days of growth in an airlift 80-mL photobioreactor, producing 7 g/L of dry biomass, and accumulated ~ 10 mg/L/day of astaxanthin, which is more than other CO₂-consuming multi-engineered systems. In addition, BC cells were cultivated in a 330-L photobioreactor to link lab-scale experiments to the industrial scale-up.

The astaxanthin volumetric productivity achieved, 10 mg/L/day, exceeds that previously reported for Haematococcus pluvialis, the standard microalgal species nowadays used at the industrial level for astaxanthin production, or for other microalgal strains engineered to produce ketocarotenoids. Overall, this work identifies a new route to produce astaxanthin on an industrial scale.