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Metab Eng. 2014 Jul;24:97-106. doi: 10.1016/j.ymben.2014.05.002. Epub 2014 May 14.

Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli.

Author information

1
Microbiology Division, IBR (Instituto de Biología Molecular y Celular de Rosario), Consejo Nacional deInvestigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Ocampo y Esmeralda, 2000 Rosario, Argentina.
2
Microbiology Division, IBR (Instituto de Biología Molecular y Celular de Rosario), Consejo Nacional deInvestigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Ocampo y Esmeralda, 2000 Rosario, Argentina. Electronic address: arabolaza@ibr-conicet.gov.ar.
3
Microbiology Division, IBR (Instituto de Biología Molecular y Celular de Rosario), Consejo Nacional deInvestigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Ocampo y Esmeralda, 2000 Rosario, Argentina. Electronic address: gramajo@ibr-conicet.gov.ar.

Abstract

Microbial fatty acid (FA)-derived molecules have emerged as promising alternatives to petroleum-based chemicals for reducing dependence on fossil hydrocarbons. However, native FA biosynthetic pathways often yield limited structural diversity, and therefore restricted physicochemical properties, of the end products by providing only a limited variety of usually linear hydrocarbons. Here we have engineered into Escherichia coli a mycocerosic polyketide synthase-based biosynthetic pathway from Mycobacterium tuberculosis and redefined its biological role towards the production of multi-methyl-branched-esters (MBEs) with novel chemical structures. Expression of FadD28, Mas and PapA5 enzymes enabled the biosynthesis of multi-methyl-branched-FA and their further esterification to an alcohol. The high substrate tolerance of these enzymes towards different FA and alcohol moieties resulted in the biosynthesis of a broad range of MBE. Further metabolic engineering of the MBE producer strain coupled this system to long-chain-alcohol biosynthetic pathways resulting in de novo production of branched wax esters following addition of only propionate.

KEYWORDS:

Branched fatty acid; Lipid metabolism; Metabolic engineering; Mycocerosic acid; Polyketide-derived molecules

PMID:
24831705
DOI:
10.1016/j.ymben.2014.05.002
[Indexed for MEDLINE]

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