The Integral Role of Bioproducts in the Growing Bioeconomy

Abstract

Bioproducts refer to industrial chemicals and materials other than fuels that are refined from renewable biological resources, or any domestic consumables manufactured with such chemicals and materials. Bioproducts development is as essential a pathway for valorizing biomass materials as biofuels. Integrated production of biofuels and bioproducts has been identified as a key strategy to improve the economics of biorefineries and the sustainability of the bioeconomy. This paper reviews the roadmap, status, and major challenges of bioproducts development. Currently there are more than 15,000 marketable bioproducts in five broad classes: biochemicals, biopolymers, bioadhesives, biomedicines, and biopesticides. These bioproducts are manufactured from diverse biomass feedstocks using biorefining technologies similar to those for biofuels. Food crops, specialty plants, lignocellulosic residues, and algal biomass can be pretreated with efficient separation techniques to extract starch, sugars, (hemi)cellulose, proteins, lipids, fibers, and specialty chemicals and further processed into valuable bioproducts through fermentation or chemical transformation. Lignocellulosic biomass can be hydrolyzed to simple sugars for manufacturing biochemicals and bioplastics via fermentation and polymerization. It can also be converted to bio-oil and syngas using pyrolysis and gasification techniques and subsequently to valuable chemicals through Fischer-Tropsch synthesis. Biowaste materials can be processed via anaerobic digestion to produce biogas, a primary industrial feedstock for numerous chemicals and plastics. The most pressing challenge of bioproducts development is to improve the economics of biorefineries through biotechnology innovations and cross-sector integration. Effective integration of biofuel and bioproducts production requires technological and financial support and life cycle assessment-based planning. The global bioproducts market value was estimated at US$282 billion in 2016 and forecast to expand annually by 11% in the next five years.

Introduction

Dwindling fossil fuel reserves and uncontrollable greenhouse gas emissions from fossil fuel consumption have driven society to transition to a bioeconomy that uses renewable biological resources (e.g., food crops, lignocellulosic biomass, algae, and biowaste materials) to produce energy and domestic consumables.¹ Globally, the bioeconomy has been fast growing in the past two decades, particularly in the production and utilization of biofuels and bioproducts. Worldwide, 108.6 billion L of bioethanol, 33.6 billion L of biodiesel, and US$8.7 billion worth of biobased chemicals were produced in 2018.^2
–4

The modern bioeconomy refers to bioproducts as industrial chemicals and materials not used for energy production and that are refined from renewable biological resources, or the domestic consumables manufactured with such chemicals and materials.⁵ Here, the term bioproducts does not cover conventional biomass-derived products such as food, fodder, fiber, lumber, pulp and paper, wood-based building materials, raw herbal medicines, and dietary supplements. The term is further distinct from biofuels in the present context, though biofuels are indeed bioproducts ( Fig. 1 ). The U.S. Department of Agriculture (USDA) identifies bioproducts as those marketable products containing at least 25wt% of biomass-derived materials.⁶

Fig. 1.

A diagram of biomass-based products, including conventional bioproducts and bioeconomic bioproducts. In modern bioeconomy, bioproducts refer particularly to biomass-derived chemicals and materials other than biofuels. Color images are available online.

The emerging bioeconomy has been centering on bioenergy development, with the conversion of biomass to various transportation biofuels as the largest and most active sector.¹ Refining biomass for bioenergy, however, generally lacks economic competitiveness due to the relatively high biomass supply and processing costs, especially when fossil fuels are at lower market prices.¹ In the U.S., for example, the failure rate of commercial advanced biofuels production projects has exceeded 50%.⁷ Fuels typically have lower market value when compared with chemicals and materials refined from the same feedstock. For instance, petrochemicals manufactured from one barrel of crude oil generate revenue averagely four times as if the same volume of crude oil was processed for fuels.⁸

Integrating bioproducts and bioenergy production has been advocated by the scientific community for achieving a sustainable biofuel industry.⁹ This strategy has also been highlighted by the US Department of Energy (DOE) for attaining a robust and resilient bioeconomy.⁸ In integrated biorefineries, biomass is processed into biofuels, biopower, bioheat, and biochemicals. Production of chemicals and materials alongside biofuels can significantly improve the overall economics of the biorefinery process by offsetting feedstock cost and increasing output value.⁸

Currently, industrial chemicals are produced predominantly from fossil resources. An international goal was established to increase the share of biological resources in chemical industry feedstocks to 30% by 2050.¹⁰ Expanded production and utilization of bioproducts creates job opportunities, reduces fossil fuel extraction and consumption and the detrimental environmental impacts (e.g., wildlife habitat destruction, air and water pollution, and greenhouse gas emissions) associated with it, and mitigates societal dependence on fossil resources. In 2016, for example, the US manufactured $157 billion worth of bioproducts (not including biopharmaceuticals, food and feed, and biofuels) through which 4.66 million jobs were created and 1.49 billion L of petroleum were replaced.¹¹ The nation is striving for a billion-ton bioeconomy, in which 1 billion dry tons of biomass feedstock is used annually to produce biofuels and bioproducts that will share 7.0% market value of the overall economy by 2030.¹²

The major challenge to this is that economically-viable conversion of biomass to valuable bioproducts requires advanced, efficient biotechnologies. Furthermore, expansion of bioproducts requires a proficient workforce and a prepared market.¹² At present, however, the general public's awareness and utilization of bioproducts remain low. There are few publications in the literature highlighting the significant role of bioproducts in the current bioeconomy and offering a roadmap of bioproducts development.

Two editorial articles describe the globally growing interest in bioproducts technologies.^13,14 Potential bioproducts based on potato (Solanum tuberosum), palm (Cocos nucifera) kernel meal, banana (Musa paradisiaca) peels, and organic waste-derived biogas are described.^15,16 This paper reviews the pathways, status, and major challenges of bioproducts development and brings together the available information on potential bioproducts derived from diverse biomass materials to increase the social awareness of bioproducts and promote the bioproducts sector of the growing bioeconomy.

Bioproducts Classification

Currently, neither a universal definition nor a widely-accepted classification system exists for bioproducts. This paper attempts to classify the available bioproducts into five broad categories: biochemicals, biopolymers, bioadhesives, biomedicines, and biopesticides, each containing different groups of candidates ( Fig. 2 ).

Fig. 2.

Classification of bioproducts into five categories and nineteen groups. Specific examples are given in each group; GMO: genetically modified organism; PHA: polyhydroxyalkanoate; PIP: plant-incorporated protectant; PLA: polylactic acid.

Biochemicals

Biochemicals refer to industrial chemicals refined from biomass materials or synthesized with those biobased intermediates. Existing biochemicals form a long list of organic acids, alcohols, aldehydes, ketones, esters, aromatics, dyes, and others ( Fig. 2 ). Examples are biomass-originated succinic acid, lactic acid, adipic acid, ethanol, 1,3-propanediol, glycerol, isoprene, phenols, ethyl lactate, and furfural.^10,17 Biochemicals have been increasingly used as industrial feedstocks to manufacture solvents, lubricants, paints, inks, cleaners, adhesives, pharmaceuticals, bioplastics, and other consumables.²

The most common biomass-derived feedstocks for producing biochemicals in commercial biorefineries are C6 (hexose)/C5 (pentose) sugars, syngas (primarily CO and H₂), and biogas (mainly CH₄).¹⁷ These feedstocks are typically prepared from biomass materials via hydrolysis, gasification, and anaerobic digestion (AD), respectively.¹ Through fermentation using genetically engineered microorganisms, plant sugars can be converted into more than 30 building block chemicals.¹⁸ Syngas from gasification of lignocellulosic biomass can be used to produce H₂, methanol, methyl esters, dimethyl ether, formaldehyde, acetic acid, and other chemicals.¹⁷ Biogas from AD of biowaste materials can be processed into numerous valuable chemicals such as methanol, acetylene, dimethyl terephthalate, hydrocyanic acid, and methylamines.¹⁹ These biochemicals are used subsequently as intermediates to produce a wide range of high-value fine chemicals and materials.²⁰

Biopolymers

Biopolymers refer to industrially synthesized polymer materials consisting of long chains of repeating, covalently bonded building units derived originally from biomass. Biopolymers include bioplastics, biofoams, biorubber, biofibers, and biocomposites ( Fig. 2 ).

Bioplastics extend to polylactic acid (PLA), polyhydroxyalkanoate (PHA), polyhydroxybutyrate (PHB), polyglycolic acid (PGA), polybutylene succinate (PBS), polycaprolactone (PCL), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), bio-polyethylene (PE), bio-polyethylene terephthalate (PET), bio-polyamide (PA), bio-polycarbonate (PC), bio-polypropylene (PP), bio-polyurethane (PU), starch blends, acetyl cellulose, cellophane, zein, and others.²¹ Among the candidates, bio-PE, bio-PET, bio-PA, and bio-PU are generally non-biodegradable while the others demonstrate certain levels of biodegradability.²² Bioplastics are manufactured from plant-derived sugars, proteins, lipids, and cellulose. Select pathways for manufacturing bioplastics are shown as in Fig. 3 . Bioplastics have been increasingly used to manufacture water bottles, shopping bags, disposable housewares, office supplies, medical devices, textiles, consumer electronics, and automotive parts.

Fig. 3.

Selected pathways for manufacturing bioplastics from various biomass materials. PLA: polylactic acid; PHA: polyhydroxyalkanoate; PHB: polyhydroxybutyrate; PA: polyamide.

Biofoams are particle foam materials prepared by processing starch, protein, cellulose, chitosan, vegetable oil, PLA, and bio-PU into a porous, sponge-like structure.²³ Biofoams function comparably to conventional petro-polystyrene and polyurethane foams in energy absorption and thermal insulation and remarkably better in water retention and pollutant-adsorption.²⁴ Biofoams have been widely utilized for packing, floating, vibration buffering, wall and attic insulation, water filtration, scouring pads, and automotive components.²³

Biorubbers are elastic polymers made from plant materials. Natural rubber, for example, is polyisoprene recovered from the milky fluid (latex) of rubber trees (Hevea brasiliensis) and the herbaceous plants guayule (Parthenium argentatum) and Russian dandelion (Taraxacum koksaghyz).²⁵ A bio-stable, biocompatible, bio-polyisobutylene-based thermoplastic elastomer invented by US scientists was approved in 2010 for use as implant materials for soft tissue replacement and reconstruction, in addition to chewing gum.²⁶ Biomimetic, biocompatible, and biodegradable elastomers, including poly(glycerol sebacate) and poly(glycerol-co-sebacic acid-co-L-lactic acid-co-polyethylene glycol), have been developed and tested for applications in tissue engineering and other medical purposes.²⁷

Biofibers refer to cellulose fibers produced by plants and to protein fibers (e.g., hair, wool, feather, and chitin) harvested from animals. Depending on the uses, biofibers are grouped into textile fibers, cordage fibers, and filling fibers. Biofibers have long been used for the production of textiles, ropes, artificial hairs, filters, electrodes, sorbents, paper, and construction and automotive parts.²⁸

Biocomposites are biofiber-reinforced polymer matrices. They are usually manufactured by incorporating plant fibers or regenerated cellulose in PLA, PHB, soy bioplastic, plasticized starch acetate, and other biopolymeric resins.²⁹ In general, biocomposites are of light weight, mechanically strong, and durable and are preferred for manufacturing surgical, construction, and automotive parts.

Bioadhesives

Bioadhesives refer to biomass-originated glue and cement products (so-called adherents) capable of holding two substrates together through surface attachment and transferring mechanical force from one substrate to the other. Bioadhesives include artificial adhesives of biological substances and natural adhesives of biopolymeric materials. Relative to conventional adhesives made from synthetic polymers in volatile organic solvents, bioadhesives are generally non-toxic and biocompatible. Some bioadhesives are applicable to special situations, such as wet environments and non-polar surfaces.

Adhesives can be synthesized from cellulose, starch, proteins, natural rubber, and natural resins. The homemade paper-binding glue, for example, is simply boiled cornstarch paste. Casein glue is prepared by dissolving milk protein in an aqueous alkaline solution.³⁰ The most common adhesive on today's market is formulated with nitrified cellulose (nitrocellulose) in organic solvents. The natural resin shellac, secreted by lac bugs (Laccifer lacca), is used commercially to produce superior-quality Shellac adhesives for jewel setting and pottery repair by dissolving the resin in ethanol. The resins secreted by conifer trees are also used to produce adhesives.³¹ Formaldehyde emissions from synthetic adhesives-based wood panels are a serious environmental concern. Manufacturing wood adhesives from lignin, tannin, starch and protein have been explored.³²

Biomedicines

Biomedicines are pharmaceutical drugs and therapeutic materials manufactured in, extracted from, or semisynthesized with biological sources. There are two broad groups of biologic medical products: Botanical medicines and biopharmaceuticals. Biocosmetics (biomass-sourced personal care products) are also listed under the category ( Fig. 2 ).

Many plants contain chemicals that have medical effects and are used for therapeutic purposes. Worldwide, 25% of prescribed drugs are of plant origin.³³ Traditional Chinese medicine includes 4,773 herbal medicines and 740 medicines made from animal ingredients.³⁴ Botanical medicines (so-called herbal medicines) are formulated with leaves, flowers, fruits, seeds, stems, barks, and roots of particular plants or their extracts and are processed into tablets, decoctions, powders, syrups, and liniments. The leaves of wormwood (Artemisia argyi), the flowers of saffron (Crocus sativus), the fruits of cocklebur (Xanthium sibiricum), and the roots of thorowax (Bupleuri radix) are example ingredients for Chinese herbal medicines.³⁴

The pharmaceutical industry has relied on plants for producing a number of drugs. For example, malaria treatments quinine and artemisinin are extracted from the bark of Cinchona trees (Cinchona spp.) and the whole plants of Sweet Sagewort (Artemisia annua), respectively.³⁵ The active ingredient paclitaxel, for anti-cancer drug Taxol, was initially discovered in the bark extracts of the Pacific Yew tree (Taxus brevifolia).³⁶

Biopharmaceuticals are medications produced using biotechnologies other than direct extraction from native biological sources. They include antibiotics, antibodies, vaccines, allergenics, hormones, interferons, blood components, tissues, viral particles, somatic cells, nucleic acids, recombinant DNA (deoxyribonucleic acid), and therapeutic recombinant proteins. The importance of biopharmaceuticals in the modern bioeconomy was highlighted by the US National Bioeconomy Blueprint.³⁷ Recombinant drugs, in particular, are produced using recombinant DNA technologies. Humulin, the first recombinant drug approved by the US Food and Drug Administration in 1982, is insulin generated by genetically modified bacteria (i.e., Escherichia coli inserted with the human insulin gene).³⁸ Today there are more than 200 approved recombinant drugs in the US, covering human insulin, hormones, antibiotics, antibodies, enzymes, vaccines, colony stimulating factors, interleukins, interferons, blood factors, and other therapeutic proteins.³⁹

A variety of personal care products, including hand soaps, deodorants, body lotions, skin moisturizers, shaving creams, perfumes, lipsticks, and shampoos have been manufactured from biological sources.⁴⁰ Animal fats, vegetable oil, plant fragrances, and other botanical ingredients are widely used to produce these biocosmetics. Compared with classical personal care products, biocosmetics are at least psychologically safer to consumers.⁴⁰

Biopesticides

Similar to biocosmetics, biopesticides do not play as significant a role as biochemicals and biopolymers in the modern bioeconomy. Because of this, they have received much less investment in research and development.⁴¹ Biopesticides can be divided into three groups: 1) biochemical pesticides that are naturally occurring substances capable of controlling pests by non-toxic mechanisms, 2) microbial pesticides consisting of microorganisms able to suppress pests, and 3) plant-incorporated protectants (PIPs) produced in genetically engineered plants from added genetic material ( Fig. 2 ). Biopesticides are effective in controlling pests and have several advantages over conventional pesticides. They are less toxic to non-target species, impose fewer pollution risks, do not induce pest resistance, and are cheaper to produce.⁴²

Biochemical pesticides are naturally-occurring substances with non-toxic modes of action (e.g., mating interference, scent attraction, and odor repellence) to target pests and demonstrate minimal toxicity to humans and the environment.⁴³ Biochemical pesticides include insect pheromones and kairomones, natural weed and insect regulators, naturally-occurring repellents and attractants, induced resistance promoters, and enzymes. Examples are limonene in citrus fruit peels, linalool in mint plants, azadirachtin in neem (Azadirachta indica) oil, and pyrethrum and pyrethrins in flowers of daisy (Chrysanthemum cinerariifolium).⁴³ Microbial pesticides use beneficial bacteria, fungi, yeasts, protozoa, and nematodes or their metabolites to control weeds and insects. The widely applied Bt microbial insecticide, for instance, contains diverse strains of the bacterium Bacillus thuringiensis (Bt) and is effective to destroy larvae of mosquito, flies, moths, and other insects. Other microbial pesticides include fungi Trichoderma spp. for controlling Armillaria rot and gray mold, the bacterium Rahnella aquatilis for controlling blue and gray molds, and the bacterium Pantoea agglomerans for controlling fireblight, Penicillium rot, and Rhizopus rot.⁴⁴ Plant-incorporated-protectants are pesticidal substances produced in genetically engineered plants. Insertion of the Bt proteins Cry1A.105 and Cry2Ab2 into the genetic material of soybean enabled the crop to produce insecticidal substances. By 2018 there were 38 active PIPs in corn (Zea mays), soybean (Glycine max), cotton (Gossypium arboreum), potato (Solanum tuberosum), and plum (Prunus spp.) in the U.S.⁴⁵

Bioproducts Technologies

Bioproducts are refined from or manufactured with biomass materials using advanced biological, chemical, and thermochemical technologies. The common biomass feedstocks for bioproducts extend to corn, sugarcane (Saccharum officinarum), sweet sorghum (Sorghum bicolor), sweet potato (Ipomoea batatas), potato, wheat (Triticum aestivum), soybean, canola (Brassica napus L.), sunflower (Helianthus annuus) seeds, flax (Linum usitatissimum), Miscanthus (Miscanthus × giganteus), switchgrass (Panicum virgatum), industrial hemp (Cannabis sativa L.), forest debris, agricultural byproducts, fungal mycelia, and algae. In biorefineries, biomass is first transformed into building block chemicals and further converted into various useful chemicals and materials using an array of bioprocessing techniques ( Fig. 4 ). Biomass-derived chemicals and materials are then used to manufacture numerous marketable bioproducts. Overall, bioproducts are cost-competitive, comparable or better in function, and normally more biodegradable when compared to their petro-based counterparts.

Fig. 4.

Common pathways and conversion technologies for producing bioproducts from biomass materials. AD: anaerobic digestion; BBCs: building block chemicals; Chem: chemical; FAME: fatty acid methyl esters; FD: fractional distillation; Ferment.: fermentation; FT Syn.: Fischer-Tropsch Synthesis; HTL: hydrothermal liquefaction; Physi: physical; Spec. Chem.: specialty chemicals; TF: transformation. Color images are available online.

Bulk biomass materials can be converted to biogas through AD ( Fig. 4 ), a widely practiced technique involving bacterial and archaeal microorganisms decomposing organic matter under O₂-limited, mesophilic (35–42°C) or thermophilic (50–55°C) temperature conditions.⁴⁶ Purification of biogas results in biomethane (CH₄), an industrial feedstock alternative to natural gas for manufacturing an array of valuable chemicals, solvents, and plastics.⁴⁷ Suitable AD feedstocks extend to animal manures, sewage sludge, food and food processing wastes, algae, and green waste. Woody biomass is generally excluded due to its low digestibility. Woody biomass can be processed using thermochemical methods such as hydrothermal liquefaction (HTL), pyrolysis, and gasification ( Fig. 4 ). In HTL, biomass feedstock is typically ground to <1 mm, transformed into 15–35% solid/water slurry, and treated under high temperature (e.g., 250–374°C), high pressure (e.g., 4–22 MPa), and O₂-free conditions for certain period of time (e.g., 30–60 min).⁴⁸ With 10–33% biomass conversion rates, the resulting biocrude oil is a mixture of numerous organic compounds and can be refined for biofuels and industrial chemicals.⁴⁹ In pyrolysis, biomass is heated at high temperature (e.g., 300–700°C) in the absence of air (O₂) to generate charcoal (biochar), bio-oil, and syngas.⁵⁰ Biochar serves as a promising soil conditioner.⁵¹ Bio-oil is a fluid similar in chemical composition to biocrude oil and can be upgraded to biofuels or refined for chemicals.¹ Syngas is an ideal source for obtaining CO, H₂, and methanol and subsequently synthesizing numerous chemical derivatives.^46,52 Gasification is aimed at maximizing syngas production by heating biomass at high temperature (e.g., 800–1200°C) with controlled O₂ supply.⁵³

Biomass materials from cultivated crops, selected natural plants, and particular algal species can be pretreated with efficient separation and purification techniques to extract the intrinsic starch, sugars, (hemi)cellulose, proteins, lipids, fibers, and specialty chemicals and further processed into various valuable bioproducts ( Fig. 4 ). The residues after extraction are subject to AD or thermochemical treatments for producing additional bioproducts ( Fig. 4 ). Lignocellulosic materials (e.g., crop residues), for example, are commonly treated with pulverization, dilute acid soaking, and enzymatic hydrolysis to recover sugars from the (hemi)cellulose components.⁵⁴ To “unlock” (hemi)cellulose from the complicated lignocellulosic structure, an array of feedstock pretreatment methods have been explored, including pulverization, freezing, ultrasound, radiation, pulsed electric field pretreatment, ionic liquid delignification, supercritical CO₂ explosion, steam explosion, ozonolysis, H₂O₂-acetic acid soaking, dilute acid pretreatment, and mild alkali pretreatment.⁵⁵ Years of research indicate that selection of pretreatment methods is feedstock-specific, and a combination of two or more of these methods is generally necessary to achieve satisfactory delignification of lignocellulosic materials.⁵⁵ To transform (hemi)cellulose to fermentable sugars, two categories of methods have mainly been evaluated: acid hydrolysis (e.g., using H₂SO₄) and enzymatic hydrolysis (e.g., using cellulases). Formulated enzyme cocktails consisting of up to 10 species of cellulases and 16 species of hemicellulases have been designed and tested to maximally recover sugars from specific lignocellulosic materials (e.g., hard wood, soft wood, switchgrass, wheat straw, and corn stover).⁵⁵ In comparison, acid hydrolysis has advantages over enzymatic hydrolysis in cost and reaction rate yet is disadvantaged in sugar recovery and environmental friendliness.⁵⁵ Considering that hemicellulose is more likely than cellulose to liberate sugars under the same conditions and pentoses are more susceptible to degradation than hexoses,⁵⁶ the hydrolysis method has to be integrative or at least compatible with feedstock pretreatment methods and subsequent sugar transformation.¹ More detailed descriptions of the biomass conversion technologies can be found in the literature.^1,46,50

Many industrial chemicals and plastics can be produced from plant-derived sugars ( Fig. 4 ). There are at least 27 building-block chemicals widely used in the chemical industry that can be produced from plant sugars by fermentation using particularly selected or genetically-engineered microbes (i.e., bacteria and yeasts) and by chemical/enzymatic transformation using specialty catalysts (Table 1). These building-block chemicals can be subsequently converted to an array of high-value new chemicals and materials. The residual lignin after sugar extraction from lignocellulosic biomass can be combusted to harvest bioenergy, gasified to generate syngas, or refined for macromolecular and aromatic chemicals.⁵⁷

Table 1.

Biological and Chemical Pathways for Potential or Commercialized Production of Building Block Chemicals from Plant Sugars^23,24,81

BUILDING BLOCK CHEMICALS	AEROBIC FERMENTATION		ANAEROBIC FERMENTATION		CHEM-ENZYME TRANSFORMATION
BUILDING BLOCK CHEMICALS	Yeast or Fungal	Bacterial	Yeast or Fungal	Bacterial	Chemical & Catalytic	Enzymatic
Three-carbon chemicals
3-Hydroxy propionic acid	X	X
Glycerol	X	X	X	X	C
Lactic acid	X		X	C
Malonic acid	X				X
Propionic acid				X
Serine	X	C
Four-carbon chemicals
3-Hydroxybutyrolactone					X
Acetoin	X	X		X
Aspartic acid	X	X				X
Fumaric acid	X	X			X
Malic acid	X	X
Succinic acid	X	X		X		X
Threonine	X	C
Five-carbon chemicals
Arabitol	X		X		C	X
Furfural					C
Glutamic acid	X	C
Isoprene		X
Itaconic acid	C
Levulinic acid					X
Xylitol	X		X	X		C
Six-carbon chemicals
2,5-Furan dicarboxylic acid					X
Aconitic acid	X
Adipic acid	X
Citric acid	C
Glucaric acid	X	X			X
Gluconic acid	C	X				X
Levoglucosan					X
Lysine	X	C
Sorbitol	X	X			C	X

X: potential; C: commercialized

Development of biopharmaceuticals relies on advanced biotechnologies. The majority of biopharmaceuticals are therapeutic recombinant protein drugs that provide critical therapies to many life-threatening diseases such as diabetes, viral hepatitis, inborn metabolism errors, and cancer treatment-related neutropenia.⁵⁸ Recombinant proteins are manufactured through recombinant DNA technology that involves isolating the DNA that encodes the target protein in humans, inserting the DNA into bacterial, fungal, or mammalian cells (e.g., E. coli, Saccharomyces cerevisiae, mouse myeloma cells, Chinese hamster ovary cells, and human fibrosarcoma cells), cultivating the genetically engineered cells, expressing and producing the protein by these cells, and then separating and purifying the protein ( Fig. 5 ). The same DNA technology can be used to develop innovative enzymes, bacteria, and yeast strains for more efficient fermentation and enzymatic transformation of biomass to bioproducts. In general, biorefining technologies for bioproducts are similar to those for biofuel production and therefore, integration of bioproducts manufacturing with biofuel production is technically feasible and economically efficient.⁸

Fig. 5.

Biotechnological procedures for developing therapeutic recombinant protein biopharmaceuticals. The graph is modified from Dingermann³⁸ and Jozala et al.⁵⁸ Color images are available online.

Refining Different Biomass Materials for Bioproducts

Potential Bioproducts from Food Crops

Sugar/starch crops (e.g., sugarcane, sweet potato, and corn) and oil crops (e.g., soybean, canola, and sunflower) are currently the primary feedstocks of the world biofuel industry. On average, barn-stored corn kernels contain 14.0% moisture, 64.5% starch, 7.6% protein, 7.7% fiber, 3.4% oil, 1.5% sugar, and 1.3% mineral ash, and soybean seeds consist of 13.0% moisture, 34.2% crude protein, 19.5% oil, 22.6% sugar/starch, 6.8% crude fiber, and 3.9% mineral ash.^59,60

In addition to bioethanol, fermentation of corn starch-derived sugar (dextrose or D-glucose) using particular bacteria and fungi can yield acetone and butanol (by Clostridium saccharobutylicum NCP 262), isopropanol (by Clostridium beijerinckii optinoii), butanediol (by Bacillus polymyxa), lactic acid (Rhizopus oryzae), acetic acid (by Clostridium thermoaceticum ATCC 49707), citric acid (by Aspergillus niger), adipic acid (by engineered S. cerevisiae), 3-hydroxypropionic acid (by engineered Escherichia coli), amino acids (by Corynebacterium glutamicum), vitamin C & E (by Bacillus endophyticus ST-1 and Ketogulonicigenium vulgare 25B-1), and food xanthan gums (by Xanthomonas campestris).^61,62 These building-block chemicals can then be used to produce an array of new chemicals, organic solvents, and bioplastics. Life cycle assessment (LCA) indicated the economic viability of bioplastics production from corn.⁶³ Distiller's dried grains with solubles (DDGS) from corn bioethanol fermentation is a high-quality animal feed.⁶⁴ The protein extracted from DDGS can be processed into zein films for food packing. Byproduct gluten meal from wet-milling-corn-ethanol refineries can be readily plasticized into a thermoplastic resin for producing biocomposites.⁶⁵

Soybean is another major feedstock for biofuels and bioproducts. Transesterification of soybean oil generates biodiesel and glycerol. Biodiesel is a mixture of numerous fatty acid methyl esters (FAME). Instead of use as a fuel, it can be separated into narrower cuts through fractional distillation and used as feedstocks for producing high-value chemicals.⁶⁶ Purified glycerol is widely used as plasticizer, moisturizer, and antifreeze. It can further be transformed to other valuable chemicals. Fermentation of glycerol using Clostridium sp. A1424 and other bacteria yields isopropanol, butanol, 2,3-butanediol, citric acid, malic acid, succinic acid, poly-γ-glutamic acid, and PHA.^67,68 Catalytic conversions of glycerol lead to 1,2-propanediol, dihydroxyacetone, acrolein, polyglycerols, and polyesters.⁶⁹ Through catalyzed chemical reactions, soybean oil can be transformed into cost-effective bio-plasticizers, bio-PA, bio-PU, and thermosetting polyester resins.⁷⁰ Fermentation of soybean oil using Ralstonia eutropha H16 and other recombinant bacterial strains generates PHA.⁷¹ Soybean oil can also be chemically transformed into polyols for manufacturing toner, paints, sealants, and urethane foam.⁷² Protein isolated from oil-free soybean meal can be used to make fire-retardant foam, casein glue alternative, wood adhesive, water-based paints, and zein polymer films.⁷³

Sugarcane-derived sugars have been used to produce bioethanol, biochemicals, bioplastics, and other bioproducts.⁷⁴ Sugarcane bagasse and leaves have been explored for producing bioethanol, biochar, methyl cellulose, furfural, xylitol, organic acids, solvents, pigments, antibiotics, and other specialty chemicals through fermentation, pyrolysis, gasification, and AD techniques.⁷⁵

Potato, sweet potato, and cassava (Manihot esculenta) are rich in starch and serve as feedstocks for bioethanol, biochemicals, and bioplastics. Potato starch is also used as a base material to manufacture drug capsules. Phenolic compounds, flavonoids, and glycoalkaloids can be recovered from potato peels by solvent extraction and used as medicines for their antibiotics, anti-allergens, antipyretics, anti-inflammatory functions.¹⁶

Fermentation of food crops using selected or genetically engineered bacteria and fungi has been practiced to produce antibiotics, vaccines, and other biopharmaceuticals.

Potential Bioproducts from Lignocellulosic Materials

Lignocellulosic biomass is composed predominantly of cellulose, hemicellulose, and lignin. Cellulose and hemicellulose can be hydrolyzed to C6/C5 sugars and then converted to biochemicals and bioplastics ( Fig. 6 ). Lignin can be converted to benzene, toluene, xylene, diacids, eugenols, syringols, cresols, and other aromatic compounds via catalyzed pyrolysis and gasification treatments.⁷⁶ Lignocellulosic materials can also be thermochemically processed via HTL, pyrolysis, and gasification to produce bio-oil and syngas that can be upgraded to drop-in biofuels and numerous valuable chemicals through the catalytic Fischer-Tropsch (FT) process.^1,77 Lignocellulosic biomass, especially herbaceous plant materials such as forage residues and green waste, can be converted to biogas via AD for further producing various biochemicals and bioplastics ( Fig. 6 ).

Fig. 6.

Production of bioproducts from lignocellulosic biomass materials using different biorefining techniques. Color images are available online.

Potential Bioproducts from Biowastes

Biowaste materials, including animal manures, sewage sludge, food-processing waste, green waste, and municipal solid organic waste, serve as feedstocks for bioenergy and bioproducts. Food-processing residues such as sugarcane bagasse, corn steep waste, rice husk, wheat bran, peanut shell, potato peels, cottonseed meal, and coconut oil cake have been used to produce various antibiotics through solid-state fermentation. Gasification of municipal solid organic waste to produce syngas and subsequent use of syngas to synthesize methanol, ethanol, and other biochemicals via fermentation or the FT process has been intensively studied and tested for economic viability.⁷⁸ Biowaste materials with high moisture content are typically processed by AD to harvest biogas, which is then purified to biomethane and used for synthesizing diverse chemicals. Biogas can also be converted to PHA through fermentation using genetically engineered bacteria.⁷⁹

Potential Bioproducts from Algae

Microalgal biomass has been evaluated as a promising feedstock for biofuels and bioproducts, though efficient cultivation of microalgae faces many challenges.¹ Algae growing in wastewater in open ponds can be processed by AD for generating biogas or by HTL for producing biocrude oil.⁸⁰ Both biogas and biocrude oil can be upgraded to biofuels, valuable chemicals, and bioplastics via catalytic conversion or fermentation techniques. Oil-producing and fast-growing algal strains cultivated in controlled environments can be extracted for algal oil, which can be transformed into biodiesel and glycerol via transesterification processing or into fatty acids, glycerol, and lipophilic substances via hydrolysis ( Fig. 7 ). The algal meal after oil extraction can be separated into proteins, carbohydrates, and pigments, or be fermented (e.g., using Clostridium saccharobutylicum NCP 262) to harvest acetone, butanol, ethanol, and other valuable chemicals.⁸¹ The residues after fermentation can be further processed by AD to produce biogas ( Fig. 7 ). At the end, the AD digestate can be applied to cropland as a soil conditioner.

Fig. 7.

Production of bioproducts from microalgae using different biorefining techniques. HTL: hydrothermal liquefaction; AD: anaerobic digestion; Catal. Conv.: catalytic conversion. Color images are available online.

Macroalgae such as seaweeds can be extracted for polysaccharides to manufacture gelling, thickening, stabilizing, and emulsifying agents (e.g., agar, alginate, and carrageenan) that are widely used in microbial research, functional food production, and textile printing.⁸²

Status and Challenges of Bioproducts Development

Development and production of bioproducts have been steadily increasing worldwide in the past decade. By 2018 there were at least 16 major bioplastics, 17 major building-block biochemicals, 70 biobased secondary chemicals and materials, and 670 approved recombinant drugs commercially produced.^21,83,84 The global bioproducts (excluding biopharmaceuticals) market expanded from $224 billion in 2013 to $282 billion in 2016 and is forecast to reach $477 billion by 2021 at a compound annual growth rate of 11.1%.⁸⁵ In 2011, world biopolymer production capacity was 3.9 million Mg. It increased to 7.2 million Mg in 2017 and would reach 9.1 million Mg by 2023.²¹ The global biochemicals market value was $8.8 billion in 2018 and is forecasted to reach $24.0 billion by 2025.² In 2017, the global biopharmaceuticals market was valued at $209 billion and is poised to grow annually at 8.5% during 2018–2023.⁸⁶

The world is transitioning from a petroleum-based economy to a biobased economy to achieve fossil fuel independence and mitigate the environmental impacts of fossil fuel consumption. More than 50 countries have established national bioeconomy strategies.⁸⁷ de Besi and McCormick conducted meta-analysis of twelve European countries' bioeconomy strategies.⁸⁸ All the strategies shared common focuses on fostering biotechnological research and innovation, optimizing biomass feedstock utilization, providing funding support for bioeconomic business development, and promoting collaboration between industry and research institutions.⁸⁸ Biotechnological research and innovation is the driver of a thriving bioeconomy that encourages new bioproducts development and more efficient biomass refining techniques.¹ Over the past decade thousands of original research papers have been published on bioproducts development from the waste residue streams (e.g., lignin, DDGS, and algal residue) of biofuel refineries.⁸⁹

Research, development, and commercial production of bioproducts are most active in North America and Europe. To support the emerging bioeconomy and the development of biomass-based industry, the US federal government enacted the Biomass Research and Development Act of 2000, through which the interagency Biomass Research and Development Board was established to create and execute the Biomass Research and Development Initiative.⁹⁰ The interagency Bioeconomy, Bioenergy, & Bioproducts (B3) Programs have been administered via the initiative to support bioeconomy research, extension, and education and boost the development of sustainable biofuel and bioproducts production systems.⁹¹ The BioPreferred program, created in 2002, has identified more than 15,000 bioproducts in 109 categories including chemicals, pharmaceuticals, lubricants, household supplies, films and packaging, safety equipment, automotive parts, and construction materials. In 2016, the US produced $157 billion of bioproducts (excluding biofuels and biopharmaceuticals), through which a total of $459 billion economic impact was generated by providing 1.68 million direct jobs and 2.98 million spillover jobs.¹¹ Bioproducts impact increased to $520 billion in 2017.⁹² A survey in 2014 revealed that there were more than 3,500 US companies manufacturing and distributing bioproducts.⁸⁵ The US bioplastic industry generated $60 million in revenue in 2016.⁸⁵ In 2018, biobased chemicals accounted for nearly 5% of the US chemical industry, with methanol, ethanol, glycerol, acetone, lactic acid, 1-butanol, and succinic acid the most common products.² The US biopharmaceutical industry accounted for 42% of global biopharmaceutical production in 2018 and generated $99 billion.⁸⁶

The European Union (EU) announced its bioeconomy strategy in 2012 to shift its economy towards “greater and more sustainable use of renewable resources.”⁹³ Through the Horizon 2020 Program, EU has been investing nearly €80 billion ($90 billion) during 2014–2020 in biotechnological innovations and public-private bioindustry partnership. In 2005, EU accounted for nearly 30% of the $77 billion global bioproducts market.⁵ An assessment by European Commission indicated that bioproducts and biofuels could generate $64 billion in annual revenue and support 3.3 million jobs in EU.⁹⁴ Therefore, EU has been promoting the bioproducts sector for “future growth, reindustrialization, and addressing societal challenges.”⁹³ The EU's knowledge-based bioeconomy sized $2.4 trillion in 2017, with Germany, Scandinavia, and Benelux the leading players.⁹⁵ In 2017, EU produced $13.5 billion worth of biochemicals and bioplastics and nearly 30% of the global market for biopharmaceuticals.^2,86

Development of bioproducts makes the bioeconomy more sustainable by expanding the utilization of renewable biological resources, creating additional job opportunities, and increasing the economic viability of biorefineries. A global transition to bioeconomy, however, involves tremendous technological, financial, and social challenges. de Besi and McCormick identified five challenged areas: (1) research and innovation, (2) biomass supply and land use, (3) economy and finance, (4) governance, and (5) social change.⁸⁸ The modern bioeconomy is powered by biotechnological innovations.¹ Breakthroughs in biomass production, conversion, and valorization will drive bioeconomic growth. It is also critical to secure sustainable biomass supply and reduce the delivered biomass feedstock costs (currently $60–80/dry ton cellulosic biomass in the US; <$50/dry ton is necessary for profitable biofuel production)¹ through wise land use management and improved biomass logistics.⁹⁶

Funding has to be made available to support biotechnology research, commercialization of biotechnological innovations, and business development of small and medium-sized bioindustry enterprises. The expanding bioeconomy and bioproducts development cannot be sustained without governmental policy coherence and institutional consistence. In addition, a transition to bioeconomy requires cooperation of all social sectors to prepare a competent workforce, supply quality feedstock materials, and establish a stable bioproducts market.¹ In particular, public awareness and market uptake of bioproducts need to be increased. Currently the most pressing challenge is to improve the economics of biorefineries and the competitiveness of bioproducts.⁹⁷ Low crude oil price impairs the economic viability of bioproducts production. Intensive research and innovation are needed to develop more efficient biomass conversion techniques and more competitive bioproducts.

The economics of bioproducts production can be further improved by removing the sector barriers and creating new value chains in the bioindustry system. Cross-sectoral cooperation and biorefining integration have been identified as a prerequisite of a successful bioeconomy.^95,98 The US bioenergy industry has recently been pursuing a model of an integrated biorefinery, in which a biofuel plant produces high-volume fuels to address domestic energy needs and while high-value organics are also manufactured to provide additional economic support for fuel production.^8,99 Indeed, integration, modularization, and upscaling of the bioindustry system are crucial to producing bioproducts superior to petroleum-based products in performance, environmental benefits, and market price.¹ Effective integration is, however, facing major techno-economic challenges, including the high capital expenditure involvements and limited options in efficient biorefining technologies and valuable bioproducts.¹⁰⁰

The US DOE reported that a promising industrial method was invented by biotechnology company Lygos, Inc. (Albany, CA) in 2015 to convert cellulosic sugars directly to malonic acid, a high-value chemical used in many manufacturing processes.⁸ The method has been tested in lignocellulosic ethanol plants for integrated production of biofuels and biochemicals.⁸ Clearly, effective biorefining integration requires research innovations and should be planned using systems thinking and LCA approaches.

Conclusions

Biofuels and bioproducts are the two pillars of the emerging bioeconomy, which is based on sustainable biomass supply and powered by biotechnological innovations. In addition to fuels, numerous chemicals and materials can be produced from biomass feedstocks in place of petroleum-based resources. The current list of bioproducts covers biochemicals, biopolymers, bioadhesives, biomedicines, and biopesticides. Biorefining technologies for bioproducts are similar to those for biofuels, including fermentation, pyrolysis, gasification, AD, and catalytic transformation. An array of high-value chemicals, plastics, composites, adhesives, and pharmaceuticals have been commercially produced from general and specialty biomass materials and used to manufacture various marketable commodities. Development of bioproducts reduces the societal dependence on fossil fuels and generates high market values that help sustain the growing bioeconomy.

Driven by biotechnological advances through intensive research, global development and production of bioproducts has been rapidly increasing during the past decade, with North America and Europe the most active regions. To date, more than 87 major industrial biochemicals and 16 major bioplastics have been commercially produced. Worldwide, the bioproducts (excluding biopharmaceuticals) market reached $282 billion in 2016 and is expanding at an annual rate of 11%.⁸⁵ In a low crude oil price environment, however, the entire bioeconomy is challenged by economic competitiveness. To improve the economics of biorefineries, research and development of more efficient biomass refining technologies and more valuable bioproducts is necessary. Cooperation between different bioindustry sectors and integration of biofuel and bioproducts production are also crucial. In particular, the integrated production of biofuels and bioproducts in a specific biorefinery has the potential to better utilize biomass feedstock, generate higher market value, and improve the bioindustry economic viability. Bioproducts are an integral part of the modern bioeconomy and play an indispensable role as crucial as biofuels. Development and production of bioproducts effectively integrated with biofuels is a key strategy to achieve a sustainable bioeconomy.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

Compilation of the overview information was financially supported by the National Natural Science Foundation of China competitive grant No. 41501188 and the USDA-AFRI competitive grants No. 2011-67009-30055 and No. 2017-67009-26770.

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