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Polyketide Synthase Engineering Toward Improved Antibiotics
Author(s) -
Schnarr Nathan A.,
Borketey Lawrence S.,
Dulaney Caroline A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb300
Subject(s) - chemical space , natural product , biochemical engineering , polyketide synthase , polyketide , computational biology , rational design , synthetic biology , combinatorial chemistry , pipeline (software) , metabolic engineering , drug discovery , chemistry , computer science , biology , microbiology and biotechnology , nanotechnology , gene , biochemistry , biosynthesis , engineering , genetics , materials science , programming language
The steady rise of drug‐resistant bacteria coupled with decreasing numbers of viable therapeutics in the pharmaceutical pipeline underscores the need for novel strategies focused on rational exploration of chemical space to design and identify the next generation of antibiotics. Polyketides and non‐ribosomal peptides make up an enormous class of natural products whose unique biosynthetic assemblies provide great potential for engineered product variation in well‐defined chemical scaffolds. Unfortunately, most attempts to generate new biologically active analogs of these molecules have suffered from poor yields largely due to inherent specificity within the enzymes responsible for their production. Using an array of chemical and biological tools, our research focuses on understanding recognition motifs leading to this selectivity to potentially improve engineering efforts at both the genetic and molecular levels. If successful, this work will permit access to a wide‐variety of important compounds based on well‐studied, natural frameworks.