Assembly of a fungal macrocyclic polylactone is catalyzed by two iterative polyketide synthases

Menisporopsin A is a bioactive macrocyclic polylactone produced by the fungus Menisporopsis theobromae BCC 4162. With the transcriptomic results during the production phase of menisporopsin A, non-reducing polyketide synthase (NR-PKS) gene namely men 1 and reducing polyketide synthase (R-PKS) gene namely men 2 are believed to participate in the menisporopsin A biosynthesis. Both genes were cloned into vectors for heterologous expression in Aspergillus oryzae NSAR1 and the transformants were analyzed using HPLC and metabolites produced were identified by NMR, HR-MS and their optical activities. Three major metabolites produced by transformants are (-)-orthosporin, (-)-6-hydroxymellein and structural derivative of menisporopsin A, ascotrichalactone A, which differs from menisporopsin A only in the presence of a keto group as highlighted in [Fig. 1]. Based on these results, we can conclude that the formation of macrocyclic polylactone requires only R and NR-PKSs and trans-acting ketoreductase is needed for the final step of menisporopsin A biosynthesis [1].

Fig. 1 Structures of (a) menisporopsin A and (b) ascotrichalactone A.

• References

• 1 Bunnak W, Wonnapinij P, Sriboonlert A, Lazarus CM, Wattana-Amorn P. Heterologous biosynthesis of a fungal macrocyclic polylactone requires only two iterative polyketide synthases. Org Biomol Chem 2019; 17: 374-379