Development of improved host-vector system for enhanced production of santalene isoforms in Azospirillum brasilense.

Engineering Azospirillum brasilense Cd to enhance FPP supply and block squalene competition increased α-santalene production by 50-fold.

• Why it matters: Limited intracellular FPP availability is a bottleneck for microbial sesquiterpene biosynthesis, and improving host-vector performance could enable higher sandalwood-oil precursor yields.
• What they did: The team disrupted the chromosomal hpnC gene, introduced heterologous Escherichia coli ispA, added extra native dxps and crtE copies, and expressed codon-harmonized santalene synthase from Santalum album.
• The result: In A. brasilense Cd, α-exo-bergamotene increased 20-fold and β-santalene increased 10-fold, and a fructose-inducible santalene synthase system was developed alongside P450-based santalol production potential.