Complete biosynthesis of vindoline and catharanthine in yeast. A total of 32 heterologous genes including CPR and CYB5 should be integrated to achieve de novo biosynthesis of vindoline and catharanthine. The whole biosynthetic pathway is divided into 3 functional modules: SAG module (shown in blue), from carbon sources to strictosidine aglycone; CAT/TAB module (shown in brown), from strictosidine aglycone to catharanthine/tabersonine; and VIN module (shown in magenta), from tabersonine to vindoline. The yellow arrows at the bottom represent genes overexpressed to enhance the supply of cofactors and transcriptional machinery. MLPLA, major latex protein-like gene A; SAM2, SAM synthetase; ZWF1, glucose-6-phosphate dehydrogenase; GAPN, nicotinamide adenine dinucleotide phosphate-dependent glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans; CPR, CYP reductase; CYB5, cytochrome b5; GAL4, transcription activator of the yeast galactose regulon. IPP, isopentenyl pyrophosphate; DMAPP, dimethylallyl pyrophosphate; GPP, geranyl pyrophosphate; FPP, farnesyl pyrophosphate.