Biosynthesis of destruxins - puzzle solved

Nonribosomal cyclopeptide destruxins were first identified from fungi in 1961. Besides their insecticidal activity, destruxins have also been explored as potential pharmaceuticals to treat cancer, osteoporosis, Alzheimer’s disease and hepatitis B. The genes responsible for their biosynthesis were a longstanding puzzle.

Prof. WANG Chengshu at the Institute of Plant and Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, and co-workers have solved this issue based on comparative genomic analysis and targeted gene disruptions. They found four clustered genes, i.e. the nonrobiosomal peptide synthetase genes dtxS1, cytochrome P450 DtxS2, aldo-keto reductase gene dtxS3 and aspartic acid decarboxylase gene dtx4, are responsible for destruxin biosynthesis in the insect pathogen Metarhizium robertsii. They also demostrated that destruxins could suppress both cellular and humoral immune responses to assist fungal propagation in insects. The differing abilities of Metarhizium species to produce toxins is dependent on the presence of the dtxS1 gene and the toxigenic species are capable of killing multiple orders of insects while the non-toxigenic Metarhizium spp. Have narrow host ranges.

Their study advanced the knowledge of fungal secondary metabolism, the mechanism of fungal entomopathogenicity and will facilitate the development of destruins as bioinsecticides or pharmaceuticals.
This work has been published on PNAS, 2012. 109(4): 1287-1292。(http://www.pnas.org/cgi/doi/10.1073/pnas.1115983109)