Cascaded valorization of brown seaweed to produce l-lysine and value-added products using Corynebacterium glutamicum streamlined by systems metabolic engineering

Seaweeds emerge as promising third-generation renewable for sustainable bioproduction. In the present work, we valorized brown seaweed to produce l -lysine, world's leading feed amino acid, using Corynebacterium glutamicum , which was streamlined by systems metabolic engineering. The mutant C. SEA-1 served a starting point development because it produced small amounts of -lysine from mannitol, major sugar, deletion its arabitol repressor AtlR and engineered pathway. Starting SEA-1, systematically optimized microbe redirect excess NADH, formed on sugar alcohol, towards NADPH, required synthesis. mannitol dehydrogenase variant MtlD D75A, inspired 3D protein homology modelling, partly generated NADPH during oxidation fructose, 70% increased yield in strain SEA-2C. Several rounds engineering further supply production. best strain, SEA-7, overexpressed membrane-bound transhydrogenase pntAB together with codon-optimized gapN encoding NADPH-dependent glyceraldehyde 3-phosphate dehydrogenase, mak fructokinase. fed-batch process, SEA-7 76 g L ?1 at 0.26 mol maximum productivity 2.1 h . Finally, integrated into valorization cascades. Aqua-cultured Laminaria digitata commercial alginate, extracted hydrolyzed enzymatically, followed recovery clean-up pure alginate gum. residual sugar-based mixture converted 0.27 C-mol SEA-7. Second, stems wild-harvested Durvillaea antarctica obtained waste processing blades human consumption, were acid treatment. Fermentation hydrolysate provided 0.40 Our findings enable improvement efficiency biorefineries tailor-made strains. • Metabolic C high-yield synthesis carbohydrate mannitol. Systems-level characterization redox metabolism impact pathway fluxes along development. Production process. First time demonstration cascaded