Recent Findings in Azaphilone Pigments

Abstract

Filamentous fungi are known to biosynthesize an extraordinary range of azaphilones pigments with structural diversity and advantages over vegetal-derived colored natural products such agile and simple cultivation in the lab, acceptance of low-cost substrates, speed yield improvement, and ease of downstream processing. Modern genetic engineering allows industrial production, providing pigments with higher thermostability, water-solubility, and promising bioactivities combined with ecological functions. This review, covering the literature from 2020 onwards, focuses on the state-of-the-art of azaphilone dyes, the global market scenario, new compounds isolated in the period with respective biological activities, and biosynthetic pathways. Furthermore, we discussed the innovations of azaphilone cultivation and extraction techniques, as well as in yield improvement and scale-up. Potential applications in the food, cosmetic, pharmaceutical, and textile industries were also explored.

Keywords: azaphilones; biotechnological tools; filamentous fungi; natural pigments; non-mycotoxigenic strains; production; regulatory issues.

Figure 10

Chemical structures of mycotoxins citrinin (102), rubratoxins A (103) and B (104), rugulovasins (105) and luteoskyrin (106) [74].

Figure 1

Source, color, constitution and global market size (GMS) data for some vegetal-originated colored compounds [25,26,27,28,29].

Figure 2

Chemical structures of Aspergillus azaphilones 1–2: sassafrin E-F; 3: sassafrinamine A; 4: trans-cavernamine; 5: cis-cavernamine; 6–10: Leu, His, Val, Arg, Trp-cavernamine derivatives; 11: hydroxy-cavernamines; 12–16: Leu, His, Val, Arg and Trp-hydroxy-cavernamines.; 17: cis-cavernine; 18: trans-cavernine; 19–20: falconensins O and P; 21–23: falconensins Q, R, and S; 24: penicitrinol Q [33,34,35,36].

Figure 3

Chemical structures of Chaetomium azaphilones: 25: Chaephilone C (1R,7S,8R,8aR,9E,11S,4′R,5′R); 26: chaephilone D; 27: chaephilone C*; 28: cochliodone J; 29: N-(3,7-Dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A; 30: 4′-epi-N-(3,7-Dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A; 31: N-(3-Methyl-2-butenyl)-2-aza-2-deoxychaetoviridin A, 32: 4′-epi-N-(3-Methyl-2-butenyl)-2-aza-2-deoxychaetoviridin A; 33: N-(3,7-Dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin E; 34: N-(3-Methyl-2-butenyl)-2-aza-2-deoxychaetoviridin E; 35: 4′,5′-dinor-5′-Deoxy-N-(3,7-dimethyl-2,6-octadienyl)-2-aza-2- deoxychaetoviridin A; 36: 4′,5′-dinor-5′-Deoxy-N-(3-methyl-2-butenyl)-2-aza-2-deoxy- chaetoviridin A; 37: seco-chaetomugilin; 38: chaetolactam A; 39: 11-epi-chaetomugilide B; 40: chaetomugilide D; 41: globusumone [37,38,39,40,41,42,43,44,45].

Figure 4

Chemical structures of Hypoxylon azaphilones: 42–45: hybridorubrins A–D; 46–47: fragirubrins F and G; 48–49: rutilins C–D; 50: 3′-malonyl-daldinin F [47,48].

Figure 5

Chemical structures of Monascus and Muyocopron azaphilones: 51: monapilonitrile; 52: monapilosine; 53: N-ethanolic monapilosine; and Muyocopron azaphilones: 54–55: muyocoprones A and B; 56: lijiquinone 1 [50,51].

Figure 6

Chemical structures of Penicillium azaphilones: 57: penicitrinone G; 58–64: Dangelones A–G; 65–66: dangelosides A and B; 67–74: didangelones A–H; 75–79: tridangelones A–E; 80: penctrimertone [52,53,54].

Figure 7

Chemical structures of azaphilones from Phomopsis: 81–83: phomopsones A–C; 84–88: tersaphilones A–E [55,56].

Figure 8

Chemical structures of azaphilones from Pleosporales: 89–90: pleosporales A and B [57].

Figure 9

Chemical structures of Talaromyces azaphilones: 91: trans-PP-O; 92–99: atrosins S (Ser),D (Asp), E (Glu), H (His), L (Leu), M (Met), Q (Gln), and T (Trp); 100–101: talaralbols A and B [32,58].

Figure 11

Monascus pigments and their chromophores (highlighted in color). Yellow: 107: monascin; 108: ankaflavin; Orange: 109: rubropunctatin; 110: monascorubrin; Red: 111: rubropunctamine; 112: monascorubramine [79].

Figure 12

Conditions reported for color-directed production of yellow, orange and red azaphilones [14,67,80,81,82,83,84,85,86,87,88,89,90].

Figure 13

Halogenated azaphilones produced by marine and terrestrial fungi. 113–114: penicilazaphilones D and E; 115: sclerotiorin; 116: N-ethylbenzene-sclerotioramine [95,96].

Figure 14

Azaphilones produced by Plenodomus influorescens in co-cultivation with Pyrenochaeta nobilis: 117: spiciferinone; 118: 8a-hydroxy-spiciferinone [102].