AbstractRemediation using micro-algae offers an attractive solution to environmental phosphate (Pi) pollution. However, for maximum efficiency, pre-conditioning of algae to induce ‘luxury phosphorus (P) uptake’ is needed. Here we show that natural pre-conditioning can be mimicked through over-expression of a single gene, the global regulator PSR1 (Myb transcription factor: Phosphate Starvation Response 1), raising P levels to 8% dry cell weight from 2% in control. Complete removal of Pioccurred in log phase, unlike the control. This was associated with increases in PolyP granule size and uptake of Mg2+, the principal counterion. Hyper-accumulation of P depended on a feed-forward mechanism, where a small set of ‘Class I’ genes were activated despite abundant external Pilevels. This drove a reduction in external Pilevels, permitting more genes to be expressed (Class II), leading to more Pi-uptake. These discoveries enable a bio-circular approach of recycling nutrients from wastewater back to agriculture.TeaserManipulating a single gene drove uptake of P and a Mg2+counter-ion for increased PolyP accumulation.