skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B 2 Biosynthesis

Abstract

Naturally occurring lactams, such as the polyketide-derived macrolactams, provide a diverse class of natural products that could enhance existing chemically produced lactams. While β-amino acid loading in the fluvirucin B 2 polyketide pathway has been proposed by a previously identified putative biosynthetic gene cluster, biochemical characterization of the complete loading enzymes has not been described. In this paper, we elucidate the complete biosynthetic pathway of the β-amino acid loading pathway in fluvirucin B 2 biosynthesis. We demonstrate the promiscuity of the loading pathway to utilize a range of amino acids and further illustrate the ability to introduce non-native acyl transferases to selectively transfer β-amino acids onto a PKS loading platform. The results presented here provide a detailed biochemical description of β-amino acid selection and will further aid in future efforts to develop engineered lactam-producing PKS platforms.

Authors:
ORCiD logo [1];  [2];  [2];  [3];  [2];  [3];  [3];  [3]; ORCiD logo [4]
  1. Agile BioFoundry (ABF), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States)
  3. Agile BioFoundry (ABF), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences (QB3) and Dept. of Chemical and Biomolecular Engineering; Technical Univ. of Denmark, Horsholm (Denmark). Novo Nordisk Foundation Center for Biosustainability
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); USDOE Office of Energy Efficiency and Renewable Energy (EERE), Bioenergy Technologies Office (EE-3B)
OSTI Identifier:
1436673
Alternate Identifier(s):
OSTI ID: 1437063
Grant/Contract Number:
AC02-05CH11231
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
ChemBioChem: a European journal of chemical biology
Additional Journal Information:
Journal Name: ChemBioChem: a European journal of chemical biology; Journal ID: ISSN 1439-4227
Publisher:
ChemPubSoc Europe
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; polyketides; biosynthesis; lactams; fluvirucin; transferase

Citation Formats

Barajas, Jesus F., Zargar, Amin, Pang, Bo, Benites, Veronica T., Gin, Jennifer, Baidoo, Edward E. K., Petzold, Christopher J., Hillson, Nathan J., and Keasling, Jay D.. Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B2 Biosynthesis. United States: N. p., 2018. Web. doi:10.1002/cbic.201800169.
Barajas, Jesus F., Zargar, Amin, Pang, Bo, Benites, Veronica T., Gin, Jennifer, Baidoo, Edward E. K., Petzold, Christopher J., Hillson, Nathan J., & Keasling, Jay D.. Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B2 Biosynthesis. United States. doi:10.1002/cbic.201800169.
Barajas, Jesus F., Zargar, Amin, Pang, Bo, Benites, Veronica T., Gin, Jennifer, Baidoo, Edward E. K., Petzold, Christopher J., Hillson, Nathan J., and Keasling, Jay D.. Fri . "Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B2 Biosynthesis". United States. doi:10.1002/cbic.201800169.
@article{osti_1436673,
title = {Biochemical Characterization of β-Amino Acid Incorporation in Fluvirucin B2 Biosynthesis},
author = {Barajas, Jesus F. and Zargar, Amin and Pang, Bo and Benites, Veronica T. and Gin, Jennifer and Baidoo, Edward E. K. and Petzold, Christopher J. and Hillson, Nathan J. and Keasling, Jay D.},
abstractNote = {Naturally occurring lactams, such as the polyketide-derived macrolactams, provide a diverse class of natural products that could enhance existing chemically produced lactams. While β-amino acid loading in the fluvirucin B2 polyketide pathway has been proposed by a previously identified putative biosynthetic gene cluster, biochemical characterization of the complete loading enzymes has not been described. In this paper, we elucidate the complete biosynthetic pathway of the β-amino acid loading pathway in fluvirucin B2 biosynthesis. We demonstrate the promiscuity of the loading pathway to utilize a range of amino acids and further illustrate the ability to introduce non-native acyl transferases to selectively transfer β-amino acids onto a PKS loading platform. The results presented here provide a detailed biochemical description of β-amino acid selection and will further aid in future efforts to develop engineered lactam-producing PKS platforms.},
doi = {10.1002/cbic.201800169},
journal = {ChemBioChem: a European journal of chemical biology},
number = ,
volume = ,
place = {United States},
year = {Fri Mar 30 00:00:00 EDT 2018},
month = {Fri Mar 30 00:00:00 EDT 2018}
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on March 30, 2019
Publisher's Version of Record

Save / Share: