Identification of targets for high penicillin G production in an industrial strain of Penicillium rubens.

To elucidate the mechanisms underlying high penicillin G (PenG) production, transcriptomic analysis was conducted on 36 samples from the reference Penicillium rubens Wisconsin 54-1255 and its industrial descendant strain IMP002. The resulting dataset was analyzed using weighted gene co-expression network analysis, yielding 26 modules that clustered genes with similar expression patterns. Three modules highly correlated with PenG production were selected to identify key hub genes, whose functions were further validated in vivo. Overexpression of the six identified hub genes, comprising one transporter gene, four regulatory genes, and one N-acetylglucosaminyltransferase gene, increased PenG production in IMP002 by 24.08% to 41.64%. Notably, overexpression of the transporter gene led to a 33.33% increase in intracellular PenG accumulation. Moreover, overexpression of the N-acetylglucosaminyltransferase gene was found to modulate the filamentation of IMP002. Our work provides an effective strategy for identifying novel targets related to high PenG production in the industrial strain. KEY POINTS: Six key targets for high PenG production were identified in the strain IMP002. Regulator, transporter, and N-acetylglucosaminyltransferase boost PenG production. WGCNA is an effective strategy for identifying novel high-yield targets.