Abstract
Isoprenoids are a large family of natural products with diverse
structures, which allow them to play diverse and important roles in the
physiology of plants and animals. They also have important commercial
uses as pharmaceuticals, flavouring agents, fragrances, and nutritional
supplements. Recently, metabolic engineering has been intensively
investigated and emerged as the technology of choice for the production
of isoprenoids through microbial fermentation. Isoprenoid biosynthesis
typically originates in plants from acetyl-coA in central carbon
metabolism, however, a recent study reported an alternative pathway, the
Isopentenol Utilization pathway (IUP), that can provide the building
blocks of isoprenoid biosynthesis from affordable C5 substrates. In this
work, we expressed the IUP in Escherichia coli to efficiently
convert isopentenols into geranate, a valuable isoprenoid compound. We
first established a geraniol-producing strain in E. coli that
uses the IUP. Then, we extended the geraniol synthesis pathway to
produce geranate through two oxidation reactions catalysed by two
alcohol/aldehyde dehydrogenases from Castellaniella defragrans.
The geranate titer was further increased by optimizing the expression of
the two dehydrogenases and also parameters of the fermentation process.
The best strain produced 764 mg/L geranate in 24 h from 2 g/L
isopentenols (a mixture of isoprenol and prenol). We also investigated
if the dehydrogenases could accept other isoprenoid alcohols as
substrates.