Production of industrial chemicals using renewable biomass feedstock is becoming increasingly important to address limited fossil resources, climate change and other environmental problems. To develop high-performance microbial cell factories, equivalent to chemical plants, microorganisms undergo systematic metabolic engineering to efficiently convert biomass-derived carbon sources into target chemicals. Over the past two decades, many engineered microorganisms capable of producing natural and non-natural chemicals have been developed. This Review details the current status of representative industrial chemicals that are produced through biological and/or chemical reactions. We present a comprehensive bio-based chemicals map that highlights the strategies and pathways of single or multiple biological reactions, chemical reactions and combinations thereof towards production of particular chemicals of interest. Future challenges are also discussed to enable production of even more diverse chemicals and more efficient production of chemicals from renewable feedstocks.

A comprehensive metabolic map for production of bio-based chemicals

Systems Metabolic Engineering Strategies: Integrating Systems and Synthetic Biology with Metabolic Engineering

A field of dreams: Lignin valorization into chemicals, materials, fuels, and health-care products

A simple method for the recovery of microbial poly(3-hydroxybutyrate) [P(3HB)] from recombinant Escherichia coli harboring the Ralstonia eutropha PHA biosynthesis genes was developed. Various acids (HCl, H2SO4), alkalies (NaOH, KOH, and NH4OH), and surfactants (dioctylsulfosuccinate sodium salt [AOT], hexadecyltrimethylammonium bromide [CTAB], sodium dodecylsulfate [SDS], polyoxyethylene-p-tert-octylphenol [Triton X-100], and polyoxyethylene(20)sorbitan monolaurate [Tween 20]) were examined for their ability to digest non-P(3HB) cellular materials (NPCM). Even though SDS was an efficient chemical for P(3HB) recovery from recombinant E. coli, it is expensive and has waste disposal problem. NaOH and KOH were also efficient and economical for the recovery of P(3HB), and therefore, were used to optimize digestion condition. When 50 g DCW/L of recombinant E. coli cells having the P(3HB) content of 77% was treated with 0.2 N NaOH at 30 degrees C for 1 h, P(3HB) was recovered with purity of 98.5%. Using this simple recovery method, the effect of recovery method on the final production cost of P(3HB) was examined. Processes for the production of P(3HB) by recombinant E. coli from glucose with two different recovery methods, surfactant-hypochlorite digestion and simple digestion with NaOH, were designed and analyzed. By employing the fermentation process that resulted in P(3HB) concentration, P(3HB) content and P(3HB) productivity of 157 g/L, 77%, and 3.2 P(3HB) g/L-h, respectively, coupled with the recovery method of NaOH digestion, the production cost of P(3HB) was US$ 3.66/kg P(3HB), which was 25% less than that obtained by employing the surfactant-hypochlorite digestion method.

Efficient and economical recovery of poly(3-hydroxybutyrate) from Recombinant Escherichia coli

Metabolically engineered Corynebacterium glutamicum for bio-based production of chemicals, fuels, materials, and healthcare products.

CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum

The textile industry has caused severe water pollution by using many toxic chemicals for producing fabric dyes. In response to this problem, indigoidine has attracted attention as an alternative na...

High-Level Production of the Natural Blue Pigment Indigoidine from Metabolically Engineered Corynebacterium glutamicum for Sustainable Fabric Dyes

Metabolic Engineering of Escherichia coli

Bio-based production of industrially important chemicals and materials from non-edible and renewable biomass has become increasingly important to resolve the urgent worldwide issues including climate change. Also, bio-based production, instead of chemical synthesis, of food ingredients and natural products has gained ever increasing interest for health benefits. Systems metabolic engineering allows more efficient development of microbial cell factories capable of sustainable, green, and human-friendly production of diverse chemicals and materials. Escherichia coli is unarguably the most widely employed host strain for the bio-based production of chemicals and materials. In the present paper, we review the tools and strategies employed for systems metabolic engineering of E. coli. Next, representative examples and strategies for the production of chemicals including biofuels, bulk and specialty chemicals, and natural products are discussed, followed by discussion on materials including polyhydroxyalkanoates (PHAs), proteins, and nanomaterials. Lastly, future perspectives and challenges remaining for systems metabolic engineering of E. coli are discussed.

Escherichia coli as a platform microbial host for systems metabolic engineering

4-Amino-1-butanol (4AB) serves as an important intermediate compound for drugs and a precursor of biodegradable polymers used for gene delivery. Here, we report for the first time the fermentative production of 4AB from glucose by metabolically engineered Corynebacterium glutamicum harboring a newly designed pathway comprising a putrescine aminotransferase (encoded by ygjG) and an aldehyde dehydrogenase (encoded by yqhD) from Escherichia coli, which convert putrescine to 4AB. Application of several metabolic engineering strategies such as fine-tuning the expression levels of ygjG and yqhD, eliminating competing pathways, and optimizing culture condition further improved 4AB production. Fed-batch culture of the final metabolically engineered C. glutamicum strain produced 24.7 g/L of 4AB. The strategies reported here should be useful for the microbial production of primary amino alcohols from renewable resources. This article is protected by copyright. All rights reserved.

Cindy Pricilia Surya Prabowo

Papers

CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum

High-Level Production of the Natural Blue Pigment Indigoidine from Metabolically Engineered Corynebacterium glutamicum for Sustainable Fabric Dyes

Metabolic Engineering of Escherichia coli

Escherichia coli as a platform microbial host for systems metabolic engineering

Microbial production of 4-amino-1-butanol, a four-carbon amino alcohol.