Engineering microbial pathways for production of bio-based chemicals from lignocellulosic sugars: current status and perspectives

Abstract

Lignocellulose is the most abundant biomass on earth with an annual production of about 2 × 10 11 tons. It is an inedible renewable carbonaceous resource that is very rich in pentose and hexose sugars. The ability of microorganisms to use lignocellulosic sugars can be exploited for the production of biofuels and chemicals, and their concurrent biotechnological processes could advantageously replace petrochemicals’ processes in a medium to long term, sustaining the emerging of a new economy based on bio-based products from renewable carbon sources. One of the major issues to reach this objective is to rewire the microbial metabolism to optimally configure conversion of these lignocellulosic-derived sugars into bio-based products in a sustainable and competitive manner. Systems’ metabolic engineering encompassing synthetic biology and evolutionary engineering appears to be the most promising scientific and technological approaches to meet this challenge. In this review, we examine the most recent advances and strategies to redesign natural and to implement non-natural pathways in microbial metabolic framework for the assimilation and conversion of pentose and hexose sugars derived from lignocellulosic material into industrial relevant chemical compounds leading to maximal yield, titer and productivity. These include glycolic, glutaric, mesaconic and 3,4-dihydroxybutyric acid as organic acids, monoethylene glycol, 1,4-butanediol and 1,2,4-butanetriol, as alcohols. We also discuss the big challenges that still remain to enable microbial processes to become industrially attractive and economically profitable.

Recent advances in the valorization of plant biomass

“…The diverse target products derived from lignocellulose feedstock can primarily be divided into three categories: monosaccharide and sugar alcohol; biodiesel; bio-oil, bio-char, and syngas, whose downstream products, such as alcohols, diols, carboxylic acids, organic acids, polymers, furfural, bio-gas, liquid alkanes and phenol [ 3 ], show diverse applications in different industries, such as pharmaceuticals, biomedical products, agrochemicals, aerospace, the building sector, filler materials, fragrances, food, cosmetics, etc. [ 98 – 102 ] All the mentioned products derived from plant biomass are listed in Fig. 4 .…”

“…In the past decade, the application of genetic and metabolic engineering in butanol-producing Clostridium has been rapidly developed [ 99 , 188 , 189 , 238 – 241 ] with the birth of ClosTron technology, which can be applied for Clostridium gene editing [ 242 , 243 ], and the discovery of the butanol-producing metabolic mechanism of Clostridium acetobutylicum ATCC 824 [ 244 ]. Additionally, genetic and metabolic engineering has also been adopted in Escherichia coli for 2,3-butanediol production [ 245 ], Neurospora crassa for itaconic acid production [ 246 ], Pseudomonas putida KT2440 for substituted styrene bioproduct production [ 247 ], and other strains for biofuel and chemical production [ 98 , 248 – 251 ]. Furthermore, some engineered microorganisms can also increase tolerance to inhibitors or upgrade lignin [ 7 , 252 ].…”

CRISPRi screens reveal genes modulating yeast growth in lignocellulose hydrolysate

“…Tab. T1) and the break down of large sugar polymers during hydrolosis pretreatment that presumably increased the concentration of fermentable carbohydrates (Sardi et al, 2016), such as galactose and mannose (Francois et al, 2020;see Methods).…”

Co-feeding glucose with either gluconate or galacturonate during clostridial fermentations provides metabolic fine-tuning capabilities

“…Surplus precursors are metabolically wasteful and deprive the cell of precious resources that could be re-directed toward growth and maintenance 6 . This excess input can lead to a production of undesired products 16,17 . Current strategies at re-direction of these excess inputs have focused on the generation of biosynthetic pathways [18][19][20] and the reconfiguration of bioreactors 21 .…”