Structure and Biosynthesis of Myxofacyclines: Unique Myxobacterial Polyketides Featuring Varying and Unprecedented Heterocycles

19 July 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


A metabolome-guided screening approach in the novel myxobacterium Corallococcus sp. MCy9072 resulted in the isolation of the unprecedented natural product myxofacycline A featuring a rare isoxazole substructure. Identification and genomic investigation of additional producers alongside targeted gene inactivation experiments and heterologous expression of the corresponding biosynthetic gene cluster in the host Myxococcus xanthus DK1622 confirmed a noncanonical megaenzyme complex as the biosynthetic origin of myxofacycline A. Induced expression of the respective genes led to significantly increased production titers enabling the identification of six further members of the myxofacycline natural product family. Whereas myxofacycline A–D display an isoxazole substructure, myxofacycline E and F intriguingly were found to contain 4 pyrimidinole, a heterocycle unprecedented in natural products. Lastly, myxofacycline G features another rare 1,2 dihydropyrol-3-one moiety. In addition to the full structure elucidation, we report the underlying biosynthetic machinery and present a rationale for the formation of all myxofacyclines. Unexpectedly, an extraordinary polyketide synthase-nonribosomal peptide synthetase hybrid was found to produce all three types of heterocycles in these natural products.


secondary metabolites

Supplementary materials

Supporting Information
Supporting Information for "Structure and Biosynthesis of Myxofacyclines: Unique Myxobacterial Polyketides Featuring Varying and Unprecedented Heterocycles"


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.