Resorcylic acid lactones are fungal polyketides that display diverse biological activities, with the potent Hsp90 inhibitor radicicol being an important representative member. Two fungal iterative polyketide synthases (IPKSs), Rdc5, the highly reducing IPKS, and Rdc1, the nonreducing IPKS, are required for the biosynthesis of radicicol in Pochonia chlamydosporia. In this study, the complete reconstitution of Rdc5 and Rdc1 activities both in vitro and in Saccharomyces cerevisiae uncovered the earliest resorcylic acid lactone intermediate of the radicicol biosynthetic pathway, (R)-monocillin II. The enzymatic synthesis of (R)-monocillin II confirmed the exquisite timing of the Rdc5 enoyl reductase domain. Using precursor-directed biosynthesis, the chemical modularity of the dual IPKS system was determined. Rdc1 readily accepted an N-acetylcysteamine thioester mimic of the reduced pentaketide product of Rdc5 to synthesize (R)-monocillin II with four additional iterations of polyketide elongation, indicating the C2′ ketone group found in (R)-monocillin II is incorporated via the functions of Rdc1 instead of Rdc5. The involvement of the thioesterase domain in Rdc1 in macrolactonization was confirmed through both site-directed mutagenesis and domain deletion. The Rdc1 thioesterase domain was also shown to be tolerant of the opposite stereochemistry of the terminal hydroxyl nucleophile, demonstrated in the precursor-directed synthesis of the enantiomeric (S)-monocillin II. Finally, reconstitution of the halogenase Rdc2 was demonstrated both in vivo and in vitro in the synthesis of pochonin D and a new halogenated analog 6-chloro, 7′,8′-dehydrozearalenol.

The iterative, highly-reducing polyketide synthases use a single copy of each domain to transform multiple substrates, defying conventional rules regarding enzyme function. Synthetic tool compounds and hybrid constructs now provide insights into the specificity of the ketoreductase in dehydrozearalenol biosynthesis. Iterative highly reducing polyketide synthases from filamentous fungi are the most complex and enigmatic type of polyketide synthase discovered to date. Here we uncover an unusual degree of programming by the hypothemycin highly reducing polyketide synthase, in which a single ketoreductase domain shows stereospecificity that is controlled by substrate length. Mapping of the structural domains responsible for this feature allowed for the biosynthesis of an unnatural diastereomer of the natural product dehydrozearalenol.

The corrosion of aluminum alloys (AA) caused by fungi has been considered as the typical reason causing the failure of aviation materials, but its corrosion mechanism is still unclear. In this work, AA 7075 corrosion induced by Fungus Aspergillus terreus with continued organic carbon starvation was investigated in artificial seawater. Results indicate that A. terreus can survive with organic carbon starvation and form a biofilm on AA surface, then accelerate AA corrosion. The pitting corrosion is more severe in biotic environments, and it is closely related to the initial spore concentration. The higher initial spore concentration, the more A. terreus survivors, leading to the more severe pitting corrosion. Acid corrosion caused by organic acids of A. terreus has no contribution to the corrosion acceleration of aluminum alloys. A. terreus can help to destroy the passive film of aluminum alloys, leading to more corrosion pits compared with the control.