Biosynthesis of odd-chain fatty alcohols in Escherichia coli

Engineered microbes offer the opportunity to design and implement artificial molecular pathways for renewable production of tailored chemical commodities. Targeted biosynthesis of odd chain fatty alcohols is very challenging in microbe, due to the specificity of fatty acids synthase for two carbon unit elongation. Here, we developed a novel strategy to directly tailor carbon number in fatty aldehydes formation step by incorporating alpha-dioxygenase (alpha DOX) from Oryza sativa (rice) into Escherichia coli alpha DOX oxidizes C-n fatty acids (even chain) to form Cn-1 fatty aldehydes (odd chain) Through combining alpha DOX with fatty acyl-acyl carrier protein (-ACP) thioesterase (TE) and aldehyde reductase (AHR), the medium odd chain fatty alcohols profile (C-11, C-13, C-15) was firstly established in E. coli. Also, medium even chain alkanes (C-12, C-14) were obtained by substitution of AHR to aldehyde decarbonylase (AD). The titer of odd chain fatty alcohols was improved from 7.4 mg/L to 101.5 mg/L in tube cultivation by means of line tuning endogenous fatty acyl-ACE TE (TesA'), alpha DOX, AHRs and the genes involved in fatty acids metabolism pathway. Through high cell density fed batch fermentation, a titer of 1.95 g/L odd-chain fatty alcohols was achieved, which was the highest reported titer in E. coli. Our system has greatly expanded the current microbial fatty alcohols profile that provides a new brand solution for producing complex and desired molecules in microbes. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.