Biotransformation of Microcystin-LR in marine sediments: Mechanism and global potential

Microcystin-LR (MC-LR), a potent hepatotoxin produced during cyanobacterial harmful algal blooms, can be transported from freshwater systems to coastal marine environments through riverine discharge and estuarine mixing, yet its environmental fate in coastal sediments remains poorly understood. Here, we investigated the biotransformation mechanism of MC-LR in coastal sediments using LC-MS/MS, metagenomics, metabolic modeling, molecular docking, and genome binning. The results showed that MC-LR was transformed primarily via co-metabolism, following pseudo-first-order kinetics. Notably, we identified a novel biotransformation pathway in the marine environment that differs from the conventionally recognized mlr-dependent pathway observed in terrestrial systems. Biotransformation in marine sediments involves peptide ring opening, formation of linear MC-LR, stepwise peptide shortening, and conversion of the Adda-containing fragment into smaller aromatic compounds. Metabolic modeling and ecological network analysis further revealed that the microbial community facilitates this co-metabolic biotransformation through a cross-feeding mechanism, in which different taxonomic groups share complementary functions for co-substrate transformation, peptide bond cleavage, and aromatic compound degradation. Metagenomic profiling and genome binning demonstrated that MC-LR transformation is coupled with glutathione metabolism, and key genes involved in MC-LR transformation (e.g., CAAX, pepA, pepN, paaA, paaG, paaZ) were mainly associated with members of the Pseudomonadota, Myxococcota, and Acidobacteriota. Global screening of publicly available MAGs revealed that CAAX genes linked to MC-LR transformation are widely distributed across aquatic environments, with 16,209 CAAX-containing MAGs identified from 498 sampling locations worldwide, including 6892 marine MAGs from 317 oceanic sites. Overall, this study clarifies the biotransformation mechanism of MC-LR in marine sediments and highlights the widespread genetic potential for its biotransformation across global aquatic environments.