New knowledge about the biosynthesis of lovastatin and its production by fermentation of Aspergillus terreus.

Lovastatin, and its semisynthetic derivative simvastatine, has great medical and economic importance, besides great potential for other uses. In the last years, a deeper and more complex view of secondary metabolism regulation has emerged, with the incorporation of cluster-specific and global transcription factors, and their relation to signaling cascades, as well as the new level of epigenetic regulation. Recently, a new mechanism, which regulates lovastatin biosynthesis, at transcriptional level, has been discovered: reactive oxygen species (ROS) regulation; also new unexpected environmental stimuli have been identified, which induce the synthesis of lovastatin, like quorum sensing-type molecules and support stimuli.

Penicillin and cephalosporin biosyntheses are also regulated by reactive oxygen species.

In an earlier work on lovastatin production by Aspergillus terreus, we found that reactive oxygen species (ROS) concentration increased to high levels precisely at the start of the production phase (idiophase) and that these levels were sustained during all idiophase. Moreover, it was shown that ROS regulate lovastatin biosynthesis. ROS regulation has also been reported for aflatoxins.