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Biological lignin valorization to fuels and value-added chemicals enables sustainable and economic biorefineries. While significant progress has been made, several major challenges arose due to high recalcitrance and heterogeneity of lignin, which needs to be addressed to improve lignin processing. This work provides an overview of biological lignin conversion and its regulation from a metabolic engineering and systems biology viewpoint. Biological lignin valorization includes three stages: lignin depolymerization, aromatics degradation, and target product biosynthesis. Ligninolytic microorganisms have an extensive enzymatic toolbox to break down the lignin and convert heterogeneous lignin derivatives to central intermediates, such as protocatechuate or catechol, through a peripheral pathway. These intermediates undergo ring cleavage via the β-ketoadipate pathway and are ultimately transformed into …