Cyanobacterial Platform for High-Value Molecules Production

JULIA ROULET; BURKART, MICHAEL D.; GOLDEN, JAMES W.; GRAMAJO HUGO; ARNAUD TATON; ARABOLAZA ANA

Conferencia; SYNBIOBETA; 2018

The development of new heterologoushosts is a key step towards producing high-value molecules in a sustainable andprofitable manner. We have developed a cyanobacterial heterologous polyketideproduction platform to enable further exploration of new polyketides encodingclusters, the production of known ones and the design-analysis of new unnaturalproducts from their sophisticated enzymes. Polyketides have numerousapplications in medicine, agriculture, and industry with annual sales of over$20B USD in the market. These compounds are promising to solve importantexisting and future global challenges; however many of them are produced by unculturableor non-genetic tractable microorganisms. Our generic and versatile platform wasconstructed using a genetically tractable and easy to grow well-establishedmodel strain of cyanobacteria, Synechococcuselongatus PCC 7942. The versatility of this system is based oninterchangeable modules harboring promiscuous enzymes for PKS activation andthe production of PKS extender units, as well as inducible circuits for aregulated expression of the PKS biosynthetic gene cluster. We have demonstrated thecapability of our new autotrophic platform to produce PKS-derived multi-methylbranched wax esters with exceptional physicochemical properties for theirapplication in the bio-lubricants, pharmaceuticals and cosmetics industries. Weare now working towards the sustainable production of high-value medicines andindustrial precursors already in the market.