Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1772-7. doi: 10.1073/pnas.1525438113. Epub 2016 Feb 1.

Metabolic model for diversity-generating biosynthesis.

Author information

1
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112;
2
Department of Biology, University of Utah, Salt Lake City, UT 84112;
3
Symbion Discovery, Inc., Salt Lake City, UT 84115;
4
Department of Chemistry, Vanderbilt University, Nashville, TN 37235;
5
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112.
6
Department of Biology, University of Utah, Salt Lake City, UT 84112; olivera@biology.utah.edu ews1@utah.edu.
7
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112; Department of Biology, University of Utah, Salt Lake City, UT 84112; olivera@biology.utah.edu ews1@utah.edu.

Abstract

A conventional metabolic pathway leads to a specific product. In stark contrast, there are diversity-generating metabolic pathways that naturally produce different chemicals, sometimes of great diversity. We demonstrate that for one such pathway, tru, each ensuing metabolic step is slower, in parallel with the increasing potential chemical divergence generated as the pathway proceeds. Intermediates are long lived and accumulate progressively, in contrast with conventional metabolic pathways, in which the first step is rate-limiting and metabolic intermediates are short-lived. Understanding these fundamental differences enables several different practical applications, such as combinatorial biosynthesis, some of which we demonstrate here. We propose that these principles may provide a unifying framework underlying diversity-generating metabolism in many different biosynthetic pathways.

KEYWORDS:

RiPP; biosynthesis; cyanobactin; natural products; secondary metabolism

PMID:
26831074
PMCID:
PMC4763782
DOI:
10.1073/pnas.1525438113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center