TitleNatural Occurrence of Hybrid Polyketides from Two Distinct Biosynthetic Pathways in .
Publication TypeJournal Article
Year of Publication2021
AuthorsZhou W, Posri P, Mahmud T
JournalACS Chem Biol
Date Published2021 02 19

Nature has always been seemingly limitless in its ability to create new chemical entities. It provides vastly diverse natural compounds through a biomanufacturing process that involves myriads of biosynthetic machineries. Here we report a case of unusual formations of hybrid natural products that are derived from two distinct polyketide biosynthetic pathways, the NFAT-133 and conglobatin pathways, in ATCC 27456. Their chemical structures were determined by NMR spectroscopy, mass spectrometry, and chemical synthesis. Genome sequence analysis and gene inactivation experiments uncovered the biosynthetic gene cluster of conglobatin in . Biochemical studies of the recombinant thioesterase (TE) domain of the conglobatin polyketide synthase (PKS) as well as its S74A mutant revealed that the formation of these hybrid compounds requires an active TE domain. We propose that NFAT-133 can interfere with conglobatin biosynthesis by reacting with the TE-domain-bound intermediates in the conglobatin PKS assembly line to form hybrid NFAT-133/conglobatin products.

Alternate JournalACS Chem Biol
PubMed ID33601889
PubMed Central IDPMC7932018
Grant ListR01 AI129957 / AI / NIAID NIH HHS / United States
S10 OD018518 / OD / NIH HHS / United States