[1S05e] 13. Microbial Engineering for Natural Products Synthesis - Part 3

4:30 PM - 5:00 PM JST(7:30 AM - 8:00 AM UTC)

[1MENP-13-KL] Structural diversity of deazapurine natural products driven by evolution of amide-forming enzymes

○Hahk-Soo Kang¹ (1. School of Advanced Biotechnology, Konkuk University (Korea))

Keywords:

Natural Products,Deazapurines,Amide-forming enzymes

Deazapurines represent a rare family of natural products. The deletion of the major antibiotic daptomycin in Streptomyces roseosporus led to the discovery of new deazapurine-derived natural products, which we named roseomycins. Biosynthetic studies of roseomycins revealed the involvement of amide bond–forming enzymes. These enzymes play a crucial role in natural product diversification by assembling complex molecules from relatively simple precursors. Two distinct classes of stand-alone amide bond–forming enzymes are typically implicated in natural product biosynthesis: ATP-grasp enzymes and amide bond synthetases. Here, we report a new family of amide bond synthetases that catalyze the formation of amide bonds between deazapurine, serving as the sole carboxylic acid substrate, and a range of amine substrates. We designate this enzyme family as deazapurine amide bond synthetases (DABS). Evolutionarily related, DABS play a central role in diversifying the structures of peptidyl deazapurine natural products. Our gene-mining analysis further reveals that most DABS-associated biosynthetic gene clusters (BGCs) remain cryptic. Thus, systematic characterization of these cryptic BGCs offers great potential for the discovery of novel peptidyl deazapurine natural products with diverse biological activities.