PacBio de novo Assembly of the Homalanthus nutans Genome Provides Insight into Prostratin Biosynthesis

The need for effective anti-HIV drugs is urgent. Over 34 million people worldwide are infected with HIV, many of whom live in countries where medicine is inaccessible due to cost. Prostratin, a natural product derived from Homalanthus nutans, a small rainforest tree grown in Samoa, is being actively developed as an adjuvant therapy to clear latent viral reservoirs, the primary obstacle to eradication of HIV. However, the current supply of prostratin is produced in limited quantities via a semi-synthetic route and the scarcity of genetic resources available for H. nutans has been significantly hampering projects targeting microbial production of prostratin.  Tissue collected from Faleolupo, Samoa, was sequenced using PacBio’s new P6C4 chemistry for ultra-long reads; although the genomic DNA was severely degraded during transit to the United States for sequencing, these technologies still provided an average read length of 10kb. While the initial genome size was estimated to be ~400Mb, BUSCO statistics indicated only ~70% of the genes were present in the first draft assembly, placing the actual genome size around 1.2Gb. The preliminary assembly has a contig N50 of 20kb. The annotated H. nutans genome sequence will facilitate identification of genes involved in prostratin biosynthesis. Once the genes are determined, they will be expressed in yeast to produce prostratin.