A photoautotrophic platform for the sustainable production of valuable plant natural products from CO2

Abstract

Many plant natural products have remarkable pharmacological activities. They are mainly produced directly by extraction from higher plants, which can hardly keep up with the surging global demand. Furthermore, the over-felling of many medicinal plants has undesirable effects on the ecological balance. In this study, we constructed a photoautotrophic platform with the unicellular cyanobacterium Synechococcus elongatus PCC7942 to directly convert the greenhouse gas CO₂ into an array of valuable healthcare products, including resveratrol, naringenin, bisdemethoxycurcumin, p-coumaric acid, caffeic acid, and ferulic acid. These six compounds can be further branched to many other precious and useful natural products. Various strategies including introducing a feedback-inhibition-resistant enzyme, creating functional fusion proteins, and increasing malonyl-CoA supply have been systematically investigated to increase the production. The highest titers of these natural products reached 4.1–128.2 mg L⁻¹ from the photoautotrophic system, which are highly comparable with those obtained by many other heterotrophic microorganisms using carbohydrates. Several advantages such as independence from carbohydrate feedstocks, functionally assembling P450s, and availability of plentiful NADPH and ATP support that this photosynthetic platform is uniquely suited for producing plant natural products. This platform also provides a green route for direct conversion of CO₂ to many aromatic building blocks, a promising alternative to petrochemical-based production of bulk aromatic compounds.