Sesterterpene ophiobolin biosynthesis involving multiple gene clusters in Aspergillus ustus

Area of Science:

• Natural Product Chemistry
• Molecular Biology
• Biochemistry

Background:

• Terpenoids are abundant natural products, but sesterterpenes, like ophiobolins, are rare, with limited understanding of their biosynthesis.
• Ophiobolins are tricyclic sesterterpenes produced by Aspergillus ustus 094102, with potential pharmaceutical applications.

Purpose of the Study:

• To elucidate the genetic basis of ophiobolin biosynthesis in Aspergillus ustus 094102.
• To identify the specific gene clusters involved in the production of ophiobolins.

Main Methods:

• Genome sequencing and in silico analysis to identify putative gene clusters.
• In vivo genetic manipulation, including gene knockout and complementation studies.
• In vitro verification of terpene synthesis enzyme function.

Main Results:

• Five gene clusters were identified and manipulated, leading to altered ophiobolin yields.
• Confirmation of the involvement of these five gene clusters in ophiobolin biosynthesis.
• Demonstration that ophiobolin skeleton biosynthesis involves gene clusters responsible for C15, C20, C25, and C30 terpenoid precursors.

Conclusions:

• Ophiobolin biosynthesis is a complex process involving at least five distinct gene clusters.
• This research provides a foundation for understanding sesterterpene biosynthesis and engineering these valuable compounds.