Phosphoproteomic Insights into the Metabolic Reprogramming of Cell Growth and Lipid Accumulation in Mucor circinelloides

Mucor circinelloides is
a model
oleaginous fungus for studying microbial lipid accumulation, yet the
post-translational mechanisms coordinating growth and lipid biosynthesis
remain poorly understood. Here, we present the first systematic quantitative
phosphoproteomic analysis of M. circinelloides across its life cycle, encompassing spores and mycelia at 6 h, 24
h (nitrogen depletion), and 96 h. A total of 1252 phosphoproteins
and 1682 phosphopeptides were identified, revealing a phosphorylation-driven
transition from growth-associated processes to lipid metabolism under
nitrogen limitation. Dynamic phosphorylation of key enzymes, notably
ATP-citrate lyase (ACL) and Acyl-CoA synthetase (ACS), directly mediated
carbon flux redirection toward fatty acid synthesis. A conserved serine-rich
motif in ACL suggests an evolutionarily conserved regulatory strategy
for lipid accumulation. Integration with fluxomics and proteomics
reveals a hierarchical network linking signaling, enzyme phosphorylation,
and metabolic reprogramming. These findings provide new insights into
phosphorylation-based regulation of fungal growth and lipid biosynthesis
in oleaginous fungi.