Growth-coupled microbial biosynthesis of the animal pigment xanthommatin
TL;DR
Imagine you want to teach bacteria to make a valuable pigment (a coloring compound) that normally comes from animals. The problem is that bacteria are usually lazy - they don't want to waste energy making something they don't need. These scientists solved this by creating a clever "deal" with the bacteria: as the bacteria make the pigment, they also produce a nutrient (formate) that they desperately need to survive and grow. It's like telling the bacteria "the more pigment you make, the more food you get." This creates a positive feedback loop where making the desired product actually helps the bacteria thrive, so they're motivated to make lots of it. The result? They can now produce gram quantities (enough to see and use) of this complex animal pigment using just sugar and engineered bacteria.
Engineering heterologous natural product pathways in bacteria has achieved broad success but most approaches suffer from low initial production levels that require extensive, resource-heavy iterative strain optimization. Xanthommatin is a structurally complex, color-changing animal ommochrome with material and cosmetic applications, yet production in microbial cell factories has been difficult. Here, we introduce a growth-coupled biosynthetic strategy involving a feedback loop where an excised one-carbon (C1) moiety is used as a driver of bacterial growth, simultaneously boosting bioproduction of the target compound. This broadly applicable, plug-and-play strategy is illustrated by enabling xanthommatin biosynthesis in a 5,10-methylenetetrahydrofolate auxotroph of the platform soil bacterium Pseudomonas putida. In this design, formate released during xanthommatin production relieves the C1 deficiency, thereby effectively coupling bacterial growth to pigment synthesis. Adaptive laboratory evolution streamlined xanthommatin's gram-scale bioproduction from glucose, establishing C1 restoration as a general biosynthetic approach to accelerate the engineering of natural product biosynthesis in bacteria.
- 1Developed a growth-coupled biosynthetic strategy using a feedback loop where an excised one-carbon moiety drives bacterial growth while boosting target compound production
- 2Successfully engineered xanthommatin biosynthesis in a 5,10-methylenetetrahydrofolate auxotroph of Pseudomonas putida by coupling formate release to growth
- 3Achieved gram-scale bioproduction of xanthommatin from glucose through adaptive laboratory evolution
- 4Established C1 restoration as a general biosynthetic approach to accelerate natural product engineering in bacteria
- 5Demonstrated that formate released during xanthommatin production relieves C1 deficiency, effectively coupling bacterial growth to pigment synthesis
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