Biosynthetic pathway connects cryptic ribosomally synthesized posttranslationally modified peptide genes with pyrroloquinoline alkaloids

TitleBiosynthetic pathway connects cryptic ribosomally synthesized posttranslationally modified peptide genes with pyrroloquinoline alkaloids
Publication TypeJournal Article
Year of Publication2016
AuthorsJordan P.A, Moore BS
JournalCell Chemical Biology
Volume23
Pagination1504-1514
Date Published2016/12
Type of ArticleArticle
ISBN Number2451-9448
Accession NumberWOS:000392842300011
Keywordsammosamides; clusters; discovery; evolution; expression; insights; leader peptide; monooxygenase; pyrroloiminoquinone; streptomyces-coelicolor
Abstract

In an era where natural product biosynthetic gene clusters can be rapidly identified from sequenced genomes, it is unusual for the biosynthesis of an entire natural product class to remain unknown. Yet, the genetic determinates for pyrroloquinoline alkaloid biosynthesis have remained obscure despite their abundance and deceptive structural simplicity. In this work, we have identified the biosynthetic gene cluster for ammosamides A-C, pyrroloquinoline alkaloids from Streptomyces sp. CNR-698. Through direct cloning, heterologous expression and gene deletions we have validated the ammosamide biosynthetic gene cluster and demonstrated that these seemingly simple molecules are derived from a surprisingly complex set of biosynthetic genes that are also found in the biosynthesis of lymphostin, a structurally related pyrroloquinoline alkaloid from Salinispora and Streptomyces. Our results implicate a conserved set of genes driving pyrroloquinoline biosynthesis that consist of genes frequently associated with ribosomal peptide natural product biosynthesis, and whose exact biochemical role remains enigmatic.

DOI10.1016/j.chembiol.2016.10.009
Student Publication: 
No
Research Topics: 
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