Periodic Reporting for period 2 - FattyCyanos (Fatty acid incorporation and modification in cyanobacterial natural products)
Reporting period: 2019-07-01 to 2020-12-31
With this in mind, the FattyCyanos project aims to:
A) develop a method to swiftly uncover fatty acid incorporating natural products in cyanobacteria and apply it to large number of cyanobacterial strains. This method should work both with and without previous information on the genetic capacity of the target cyanobacterium to produce such compounds.
B) study the biosynthesis of selected fatty acid-incorporating and -modifying natural products, to reveal unusual biocatalytic transformations and the enzymes that catalyze them.
Furthermore, we have studied the biosynthesis of the bartolosides and revealed a biocatalytic transformation, mediated by the enzyme BrtB, which was until then only known in synthetic chemistry. This enzymatic reaction is a new type of biological esterification in which the fatty acids are esterified to a halogenated carbon. Most strikingly, the fatty acids react as free carboxylates and therefore bypass what was thought was a universal requirement: fatty acid activation.
Finally, we have critically reviewed the literature on the alkylresorcinol-type of fatty acid-incorporating metabolites. We looked into the entire diversity of these compounds in cyanobacteria and identified opportunities for discovery of new metabolites and enzymes.
Our discovery of BrtB and of its unprecedented reactivity, will enable additional explorations of the chemical and biosynthetic space associated with members of this fatty acid-acting enzyme class. Furthermore, our continuing biosynthesis studies on selected fatty acid incorporating metabolites is expected to reveal new biochemical transformations and new enzymes.
Our findings to date and anticipated future discoveries will overall lead to a better understanding of the utilization and modification of fatty acids in cyanobacterial secondary metabolism and facilitate natural products discovery efforts in these organisms.