Monascus pigments (MPs) are important azaphilone-type polyketide pigments, yet yield control, stability, and safety pose challenges. Using an epigenetic derepression strategy, we constructed an Ash2 deletion mutant in the acidophilic fungus Talaromyces purpurogenus OUCMDZ-019, with Ash2 being a COMPASS subunit involved in H3K4 methylation. Transcriptomic analysis revealed broad transcriptional changes, including marked upregulation of an MPs-related BGC, accompanied by pronounced metabolome remodeling. Integrating genome mining, transcriptomics, and GNPS molecular networking enabled targeted isolation of twelve MP derivatives, including four new azaphilones (talarpurpurones A–D), whose absolute configurations were confirmed by spectroscopy. pH-dependent transformation experiments clarified the behavior of azaphilic addition, providing insight into pigment interconversion and composition drift during fermentation. Talarpurpurone A exhibited high color value and stable red coloration from pH 3 to 11, outperforming commercial preparations. These pigments displayed selected moderate activity against Gram-positive bacteria and lipid-lowering activity. Notably, bioinformatic and fermentation analysis supported the absence of citrinin biosynthesis in OUCMDZ-019. Overall, these results suggest that Ash2 deletion is associated with azaphilone pigment diversification in Talaromyces under the tested conditions and provide a citrinin-free fungal strain for MPs production.

Phenazine derivatives, a class of naturally occurring antibiotics primarily produced by bacteria, are regarded as promising scaffolds for developing new antibiotics. In this study, eight new dimeric phenazine derivatives, phenazostains K‒R (1‒8), along with two reported dimeric analogues, phenazostains B (9) and C (10), were isolated from the fermentation broth of the marine-derived Streptomyces sp. OUCMDZ-4923. Their structures were elucidated through spectroscopic analysis, primarily using NMR and HRESIMS spectra, ECD calculations, and the modified Mosher's method. Compounds 1‒10 feature the 12-deoxysaphenate unit linked to various sites on methyl saphenate, phenazine, or methyl phenazine-1-carboxylate. Notably, compounds 1 and 2 represent the first dimeric phenazines linked by a 12, 12'-oxy bridge. Our experimental results suggest that these dimers could be formed from methyl saphenate (12) through a nonenzymatic pathway. Moreover, the analysis of gene roles within their biosynthetic gene cluster revealed that phenazostains 1‒8 are formed through a nonenzymatic process. Additionally, all dimers were evaluated for their antibacterial activity; compounds 1, 3‒5, and 9 exhibited inhibitory activities against both Staphylococcus aureus and its methicillin-resistant strain (MRSA), with MIC values ranging from 1.56 to 25.0 μg/mL.