Golden Rice-Lessons learned for inspiring future metabolic engineering strategies and synthetic biology solutions

Golden Rice is a genetically modified rice variety that accumulates carotenoids with provitamin A activity in its endosperm. This biofortified crop was developed to fight provitamin A deficiency prevailing in countries with a diet based on rice as the major staple. Since its first version in 2000, Golden Rice was continuously developed to increase endosperm carotenoids, to achieve regulatory compliance, and to introgress the trait into regional rice varieties. Golden Rice was recently approved for planting in the Philippines. In this review, we recapitulate major steps leading to the current version of Golden Rice. We examine the knowledge regarding the carotenoid pathway and the technical capabilities to generate transgenic plants at each development stage. Moreover, we discuss whether the scientific approaches taken at the time would be any different today with the increased knowledge and analytical capacities available. We conclude that most decisions for each Golden Rice version would be very similar which is due to the peculiarities and the complexity of the carotenoid biosynthetic pathway. However, each step taken in the development of Golden Rice yielded much insight about regulation of the carotenoid pathway in plants as well as into specific requirements in rice endosperm. The knowledge gained and the recent advances in the field can provide strategies and molecular tools, including synthetic biology approaches, to help develop future versions of Golden Rice with improved provitamin A levels and carotenoid storage capabilities of the rice endosperm.