Insights into heterocyclization from two highly similar enzymes.
The cyanobactin biosynthetic pathways pat and tru, isolated from metagenomes of marine animals, lead to diverse natural products containing heterocycles derived from Cys, Ser, and Thr. Previous work has shown that PatD and TruD are extremely broad-substrate heterocyclase enzymes. These enzymes are virtually identical in their N-terminal putative catalytic domains, but only approximately 77% identical in their C-terminal putative substrate-binding domains. Here, we show that these differences allow the enzymes to control regioselectivity of posttranslational modifications, helping to control product chemistry in this hypervariable family of marine natural products.
McIntosh
John A
JA
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Donia
Mohamed S
MS
Schmidt
Eric W
EW
D000595:Amino Acid Sequence; D029681:Arabidopsis Proteins; D000458:Cyanobacteria / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006571:Heterocyclic Compounds / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry*; D049294:Phospholipid Transfer Proteins; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity
D029681:Arabidopsis Proteins; D006571:Heterocyclic Compounds; C494623:PATL1 protein, Arabidopsis; D010456:Peptides, Cyclic; D049294:Phospholipid Transfer Proteins