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This content will become publicly available on March 30, 2019

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

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:
Grant/Contract Number:
AC02-05CH11231
Type:
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
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)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; polyketides; biosynthesis; lactams; fluvirucin; transferase
OSTI Identifier:
1436673
Alternate Identifier(s):
OSTI ID: 1437063