Exploring the biosynthesis of natural products and their inherent suitability for the rational design of desirable compounds through genetic engineering.
Much effort has been invested in studying how natural products are biosynthesized, and great advances have been made in understanding how these compounds acquire their structural complexity and biological activities. In recent years, significant progress has been made due to the devoted efforts of scientists in this field and to technological advancements. Numerous details, applications, and innovative findings have been elucidated by scientists using biochemical, genetic, and molecular biological approaches. Here I present a comprehensive overview of highly valued biosynthetic proteins, polyketide synthase and nonribosomal peptide synthetase. I begin with "Diels-Alderase" a captivating enzyme that has the ability to catalyze a Diels-Alder reaction valued by chemists for its usefulness in chemical synthesis. A handful of these enzymes have been characterized and chemically authenticated. The most well understood enzyme of this category is macrophomate synthase. Secondly, I focus on the polyketide and nonribosomal peptide biosynthetic pathways and the enzyme assembly for producing its metabolite. Many important natural products are produced by this biosynthetic pathway as secondary metabolites, such as erythromycin, rifamycin, and FK520, as antibiotics and an immunosuppressive, respectively. I conclude with a discussion of nonribosomal peptides and their mechanistic pathways. Special attention will be devoted to de novo production of echinomycin in a heterologous manner, the earliest example of totally engineered biosynthesis of the biologically active form of a nonribosomal peptide host in Escherichia coli.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA. kenjiwat@usc.edu
Kenji
K
Watanabe
D001363:Awards and Prizes; D001688:Biological Products / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005818:Genetic Engineering / Q000379:methods*; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism
D001688:Biological Products; D018942:Macrolides; D010455:Peptides; D004247:DNA