Growth-coupled Microbial Biosynthesis of the Animal Pigment Xanthommatin

Growth-coupled bioproduction is a powerful approach for engineering biosynthetic pathways by linking production of a target compound to cell survival. I will present a one-carbon based growth-coupling design and demonstrate its application towards production of the color-changing animal pigment xanthommatin in the bacterial host Pseudomonas putida. Cellular metabolism was rewired to block biosynthesis of the essential cofactor 5,10-methylene-THF from glucose and enable its biosynthesis from formate, a byproduct of the conversion of tryptophan to xanthommatin. This resulted in higher titer relative to the wildtype host carrying the same pathway and facilitated adaptive laboratory evolution to streamline gram-scale production of xanthommatin.