Insights into fluorometabolite biosynthesis in Streptomyces cattleya DSM46488 through genome sequence and knockout mutants

Streptomyces cattleya DSM 46488 is unusual in its ability to biosynthesise fluorine containing natural products, where it can produce fluoroacetate and 4-fluorothreonine. The individual enzymes involved in fluorometabolite biosynthesis have already been demonstrated in in vitro investigations. Candidate genes for the individual biosynthetic steps were located from recent genome sequences. In vivo inactivation of individual genes including those encoding the S-adenosyl-l-methionine:fluoride adenosyltransferase (fluorinase, SCATT_41540), 5′-fluoro-5′-deoxyadenosine phosphorylase (SCATT_41550), fluoroacetyl-CoA thioesterase (SCATT_41470), 5-fluoro-5-deoxyribose-1-phosphate isomerase (SCATT_20080) and a 4-fluorothreonine acetaldehyde transaldolase (SCATT_p11780) confirm that they are essential for fluorometabolite production. Notably gene disruption of the transaldolase (SCATT_p11780) resulted in a mutant which could produce fluoroacetate but was blocked in its ability to biosynthesise 4-fluorothreonine, revealing a branchpoint role for the PLP-transaldolase.

Graphical abstractGene knockouts in S. cattleya confirm the role of individual genes involved in fluorometabolite biosynthesis.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Gene knockout experiments. ► Genome sequence of S. cattleya. ► 4-FT acetaldehyde transaldolase knockout. ► flH antiporter not involved in fluorometabolism.