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

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 t...

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Bibliographic Details
Published in:Metabolic engineering 2014-07, Vol.24, p.97-106
Main Authors: Menendez-Bravo, Simón, Comba, Santiago, Sabatini, Martín, Arabolaza, Ana, Gramajo, Hugo
Format: Article
Language:English
Subjects:
Acyltransferases - biosynthesis
Acyltransferases - genetics
Branched fatty acid
Carbon-Sulfur Ligases - biosynthesis
Carbon-Sulfur Ligases - genetics
Escherichia coli
Escherichia coli - enzymology
Escherichia coli - genetics
Esters - metabolism
Fatty Acids - metabolism
Lipid metabolism
Metabolic Engineering
Mycobacterium tuberculosis
Mycocerosic acid
Polyketide-derived molecules
Polyketides - metabolism
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Summary: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. •Engineering of the M. tuberculosis mycocerosic acid biosynthesis pathway in E. coli.•Production of a broad range of multi-methyl-branched fatty acid derived esters.•De novo biosynthesis of methyl-branched waxes with the only addition of propionate.
ISSN:1096-7176
1096-7184
DOI:10.1016/j.ymben.2014.05.002