Abstract
To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms, development of new, versatile, bio-based production platforms is required. Here we present a novel yeast-based platform for biosynthesis of bacterial aromatic polyketides. The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host.
Highlights
An increasing number of chemicals are being produced by environmentally-friendly bio-based synthesis [1,2] to overcome the problems of low-yielding chemical synthesis or solvent-heavy extraction from natural resources, for achieving a sustainable way of life
The 8/9 ketides were the most abundant type II polyketides among sequenced bacteria, we further decided to concentrate on producing octaketides in yeast
LC-MS analysis revealed that detected metabolites are the Med pathway intermediates in both strains with 2–4 enzymatic steps replaced by enzymes from Med pathway (Fig. 4B; TC-175, TC-177). These results indicate that the developed platform system can be potentially reprogrammed and employed for production of diverse bacterial polyketide compounds
Summary
An increasing number of chemicals are being produced by environmentally-friendly bio-based synthesis [1,2] to overcome the problems of low-yielding chemical synthesis or solvent-heavy extraction from natural resources, for achieving a sustainable way of life. Production of natural products, such as polyketides, in heterologous hosts has often proven difficult or even impossible [5,6,7]. To overcome these limitations, standardized, versatile and programmable biosynthesis platforms in genetically tractable and robust hosts are desired. Polyketides have been, and still are, major leads in drug discovery programs [11,12,13,14]
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