Fig. 1

Engineered biosynthetic pathway in Synechocystis sp. PCC 6803. In our model cyanobacteria, the taxol heterologous synthesis pathway starts from the isoprenoid universal precursors IPP and DMAPP (provided by the native MEP pathway) to generate GGPP, then taxadiene and small amounts of its isomer iso-taxadiene. Under the catalysis of P450 oxidase (T5αH) and its cognate reductase (CPR), taxadiene is oxidized into a series of oxygenated taxanes (as shown in orange square), of which the specific product T5α-ol will undergo multiple rounds of stereospecific oxidations, acylations, and benzoylation to form Taxol (as shown in black dashed square). Genes highlighted in red represent heterologous genes that have been overexpressed through genome integration. G3P: glyceraldehyde-3 phosphate, DXP: deoxyxylulose 5-phosphate, MEP: methylerythritol 4-phosphate, HMBPP: (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate, IPP: isopentenyl diphosphate, DMAPP: dimethylallyl diphosphate, DXS: 1-deoxyxylulose-5-phosphate synthase, IspA: farnesyl phosphate synthase, GGPPS: geranylgeranyl diphosphate synthase, TASY: taxadiene synthase, T5αH: taxadiene-5α-hydroxylase, CPR: cytochrome P450 reductase