Synthesis of chemicals by metabolic engineering of microbes

Abstract

Metabolic engineering is a powerful tool for the sustainable production of chemicals. Over the years, the exploration of microbial, animal and plant metabolism has generated a wealth of valuable genetic information. The prudent application of this knowledge on cellular metabolism and biochemistry has enabled the construction of novel metabolic pathways that do not exist in nature or enhance existing ones. The hand in hand development of computational technology, protein science and genetic manipulation tools has formed the basis of powerful emerging technologies that make the production of green chemicals and fuels a reality. Microbial production of chemicals is more feasible compared to plant and animal systems, due to simpler genetic make-up and amenable growth rates. Here, we summarize the recent progress in the synthesis of biofuels, value added chemicals, pharmaceuticals and nutraceuticals via metabolic engineering of microbes.

Fungi as a source of natural coumarins production

“…Microorganisms such as Saccharomyces cerevisiae, Bacillus strains, Streptomyces strains, Corynebacterium glutamicum, and Aspergillus oryzae are selected as a host for fermentations depending on their specific metabolic pathways to synthesize target products (Vannelli et al 2007;Hara et al 2014;Sun et al 2015). Coumarin synthesis using metabolic engineering allows to better identify the reactions and enzymes involved in the process and to increase the likelihood of developing effective strategies with the goal of large-scale manufacture.…”

“…Endogenous metabolites chorismate and malonyl-CoA were converted to 4-HC via salicylate. The semisynthesis of warfarin was performed indicating 43.7 ± 2.6 mg L −1 warfarin with molar yield of 4.6 % (Lin et al 2013a;Sun et al 2015). 4HC is commonly used to treat thromboembolic diseases (Mueller 2004;Lin et al 2013a;Molina and Zanusso Júnior 2014) and serves as an immediate precursor of these synthetic anticoagulants (Lin et al 2013a).…”

“…Metabolic engineering and synthetic biology have enabled the construction of novel metabolic pathways that do not exist in nature or enhance existing ones (Sun et al 2015). Microorganisms such as Saccharomyces cerevisiae, Bacillus strains, Streptomyces strains, Corynebacterium glutamicum, and Aspergillus oryzae are selected as a host for fermentations depending on their specific metabolic pathways to synthesize target products (Vannelli et al 2007;Hara et al 2014;Sun et al 2015).…”

“…Some PAL enzymes convert L-phenylalanine (3) for CA (4) and the Cytochrome P450 enzyme cinnamate 4-hydroxylase (C4H) hydroxylates at the para position to produce pHCA (11). When tyrosine (10) is used as substrate, trans-pHCA (11) is produced in one step and is accomplished by phenylalanine ammonia-lyase (PAL)/tyrosine ammonia-lyase (TAL) (Vannelli et al 2007;Sun et al 2015). The gene from yeast Rhodotorula glutinis, screened for their ability to produce the PAL/TAL enzyme with high TAL activity, was cloned and expressed in Escherichia coli for the production of pHCA (Vannelli et al 2007).…”

Analysis of the genomic sequences and metabolites of Serratia surfactantfaciens sp. nov. YD25T that simultaneously produces prodigiosin and serrawettin W2

“…Serrawettin W1 is a symmetric dilactone structure composed of two serine residues connected with two 3-hydroxydecanoic acids [13]. It has been regarded as a good anti-cancer drug, which could inhibit cell growth and induce apoptosis of several cell lines derived from T-cell leukemia or Burkitt lymphoma [14, 15]. Serrawettin W2 contains a fatty acid connected with five amino acid residues, which was first isolated from S. marcescens in 1986 [16].…”