Connect DNA sequence space with chemical manufacture

	Genetically manipulate well-characterized biosynthetic pathways
	Elaborate unknown biosynthetic pathways
	Combine genes from different organisms to create new biosynthetic pathways
	Functionally integrate chemical catalysis and microbial catalysis

	Microbes have been constructed for the synthesis of shikimic acid and aminoshikimic acid
	A microbial synthesis of phloroglucinol has been established
	Biosynthetic pathways have been created for synthesis of 1,2,4-butanetriol
	Catalytic deoxygenation of phloroglucinol affords resorcinol
	Chemical conversion of L-lysine into caprolactam has been achieved

	Microbial synthesis of shikimic acid is commercially used for Tamiflu manufacture.  Routes for the chemical synthesis of Tamiflu from aminoshikimic acid have been delineated
	Microbial synthesis of phloroglucinol establishes a U.S. source for the starting material needed for manufacture of the explosive 1,3,5-triamino-2,4,6-trinitrobenzene
	Microbial synthesis of 1,2,4-butanetriol provides access to a starting material needed for the manufacture of the energetic plasticizer 1,2,4-butanetriol trinitrate
	Chemical conversion of phloroglucinol into resorcinol establishes an alternative to routes currently used for the manufacture of this pseudocommodity chemical
	The goal of manufacturing nylon 6 from renewable feedstocks has been brought closer to commercial reality

Abstract:

Metabolic engineering can serve in a variety of different roles in industrial chemistry.  Semisynthetic approaches used in the manufacture of pharmaceutical agents can recruit metabolic engineering to access molecules possessing unique chemical functionality and/or a high density of stereocenters.  Examples include shikimic acid and aminoshikimic acid, which are starting materials used for synthesis of the antiinfluenza drug Tamiflu.  Microbial synthesis of shikimic acid follows from manipulation of a well-characterized biosynthetic pathway.  Elaboration of a previously uncharacterized biosynthetic pathway provides the basis for microbial synthesis of aminoshikimic acid.  Phloroglucinol and 1,2,4-butanetriol, which are starting materials used in the manufacture of energetic materials, exemplify chemicals that are difficult to chemically synthesize that are amenable to microbial synthesis.  Discovery of its intermediacy in an incompletely characterized biosynthetic pathway provides the basis for microbial synthesis of phloroglucinol.  By contrast, microbial synthesis of 1,2,4-butanetriol follows from the creation of a biosynthetic pathway that does not exist in nature.  Resorcinol and caprolactam are chemicals currently manufactured from petroleum that can now be synthesized from renewable feedstocks by interfacing microbial and chemical catalysis.  Catalytic deoxygenation of microbe-synthesized phloroglucinol affords resorcinol while cyclization and deamination of microbe-synthesized L-lysine leads to caprolactam.  Resorcinol is a monomer used in adhesive and resin formulations.  Polymerization of caprolactam affords nylon 6.

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