Xin Wang,Siyuan Gao,Jing Wang,Sheng Xu,Hui Li,Kequan Chen,Pingkai Ouyang,*

1 State Key Laboratory of Materials-Oriented Chemical Engineering,College of Biotechnology and Pharmaceutical Engineering,Nanjing Tech University,Nanjing 211816,Jiangsu,China

2 Zhejiang Zhongshan Chemical Industry Group Co.Ltd,Huzhou 313100,China

ABSTRACT Bio-based diamines are considered to be a promising alternative to traditional fossil-fuel-based diamines,the important platform chemical for the synthesis of polymer materials.In this review,the current status of the art of the synthesis of aliphatic and aromatic diamines from renewable biomass are considered.In the case of aliphatic diamines,we describe strategies for biologically producing diamines with different carbon numbers including 1,3-diaminopropane,1,4-butanediamine,1,5-pentanediamine,1,6-diaminohexane,1,8-diaminooctane,1,10-diaminodecane,and 1,12-diaminododecane.In addition,aromatic diamines produced from various kinds of renewable biomass,including lignin,cashew nut shell,and terpenoids,are reviewed here.Furthermore,the application of typical diamines in synthesis of polyurethane and polyamide are also reviewed.

Keywords:Aliphatic diamines Aromatic diamines Polyamide Polyurethane

1.Introduction

Diamines have been widely used as the monomer for the synthesis of polyurethane,polyamide and other macromolecule materials[1,2].Among them,The global market demand in polyamides was expected to reach a total of 9.7 million tons in 2020[3].Polyurethane is also widely used in foam plastics,adhesives,coatings and fibers with an annual consumption of nearly 300,000 tons.The broad market for these macromolecule materials has increased the demand for a supply of the monomers.These monomers have been traditionally produced from non-renewable petroleum through chemical processing.With the rising concerns over the global petroleum crisis and climate change,the development of sustainable polymers is important for the modern macromolecular chemistry.The bio-based production of diamines from renewable biomass to replace fossil-fuel-based diamines for the synthesis of polymer has attracted increasing attention from the economic and ecologic perspectives.

Nowadays,the synthetic routes of the bio-based aliphatic and aromatic diamines from biomass have been developed.Aliphatic diamines were mainly produced in biotechnology via the fermentation,whole cell bioconversion or the enzymatic processes [4–6].To improve microbial production of aliphatic diamines,different engineering strategies have been explored,including heterologous gene expression [7–11],protein engineering [12–15],enhancement of metabolic flux to targeted products by key gene overexpression or deletion of byproduct pathway [11,16],transporter engineering to improve mass transfer[17,18],improvement of cofactor supply [19,20],and others.For the production of biobased aromatic diamines,several chemical synthesis routes with the renewable biomass as starting materials were also developed[21–23].On the basis of these works,several engineered microorganisms,enzymes or routes capable of efficiently producing diamines have been obtained.

As the advantages of diamines,this review systematically introduces the strategies to production of bio-based diamines.The biological production of aliphatic diamines with different carbon numbers including1,3-diaminopropane,1,4-diaminobutane,1,5-diaminopentane,1,6-diaminohexane,1,8-diaminooctane,1,10-diaminodecane,and 1,12-diaminododecane were described here.In addition,aromatic diamines that could be produced from renewable biomasses of lignin,cashew nut shell,and terpenoids,are reviewed here.The application of typical diamines is also discussed.

2.Aliphatic Diamines

In this section,recent studies describing strategies for production of bio-based aliphatic diamines are discussed (Fig.1A and B).

Fig.1.The synthesis of bio-based aliphatic diamines.(A) The synthesis of 1,3-diaminopropane,putrescine,cadaverine from renewable biomass;(B) The synthesis of 1,6-diaminohexane,1,8-diaminooctane,1,10-diaminodecane,and 1,12-diaminododecane from renewable biomass.

2.1.1,3-Diaminopropane

1,3-Diaminopropane (1,3-DAP),a C3 diamine,could be used as a building block for polyamide,cross linker for epoxy resins,and precursor for pharmaceuticals,agrochemicals and organic chemicals[24].In some microorganisms,such asPseudomonasandAcinetobacterspecies,the production of 1,3-DAP has been detected at a physiological level[25,26].Two natural pathways for 1,3-DAP synthesis was characterized,including the C4 pathway inAcinetobacter baumanniiand the C5 pathway inPseudomonas aeruginosa.In the C4 pathway,L-aspartate was used as the precursor to generate L-aspartate semialdehyde,which was then converted to 1,3-DAP by 2-ketoglutarate 4-aminotransferase and L-2,4-diaminobutanoate decarboxylase encoded by thedatandddcgenes,respectively[26,27].In the C5 pathway,using L-glutamic acid as a precursor,putrescine was synthesized through the ornithine or arginine pathway,and then converted to spermidine by spermidine synthase SpeE.Subsequently,the spermidine dehydrogenase encoded by geenspdHcatalyzed the spermidine to generate 1,3-DAP [25].

Of the two aforementioned 1,3-DAP synthetic pathways,the Laspartate 4-semialdehyde-dependent pathway is thought to be more efficient since theS-adenosyl-3-methylthiopropylamine(dAdoMet) was required as a co-substrate in the 1,4-DABdependent pathway [10].AL-aspartate 4-semialdehydedependent pathway was constructed inE.colithrough the heterologous expression of DAT and DDC fromA.baumanniifor the synthesis of 1,3-DAP [10].A titer of 13 g·L-11,3-DAP was achieved a fed-batch fermentation by the final engineeredE.coli.This report has opened new avenues for the development of engineered microorganisms to produce 1,3-DAP.

2.2.1,4-Diaminobutane

1,4-Diaminobutane (1,4-DAB) could be widely used in the industrial production of bioplastics,pharmaceuticals,agrochemicals,and surfactants.The demand for 1,4-DAB is approximately 10,000 tons per year [28].1,4-DAB biosynthesis occurs in a wide range of organismsviaL-arginine or L-ornithine.In the Lornithine pathway,1,4-DAB was produced through a one-step reaction catalyzed by L-ornithine decarboxylase ODC [11].As an alternative pathway,L-arginine decarboxylase ADC catalyzes the formation of agmatine from L-arginine,which is then converted to 1,4-DAB by agmatinase encoded byspeB[11].For the bioproduction of 1,4-DAP,several efforts have been made inE.coliorC.glutamicum.In 2009,Qianet al.[16]first metabolically engineeredE.colito produce 1,4-DAB.The engineered stain featured inactivation of the 1,4-DAB utilization pathways,deletion of the L-ornithine carbamoyltransferase chain I,overexpression of genes involved in ornithine biosynthesis,and deletion of the transcriptional factor RpoS.24.2 g·L-1of 1,4-DAB was produced by the final engineeredE.coliwith a productivity of 0.75 g·(L-1·h-1)based on a fed-batch process [16].Subsequently,a fine-tuned gene knockdown system via modulation of synthetic small RNA (sRNA)expression levels was developed.The repression ofglnAandargFenhanced the production of 1,4-DAB to 42.3 g·L-1during fedbatch culture,which is the highest 1,4-DAB titer achieved inE.coli[29].

C.glutamicumis also a promising host for 1,4-DAB production due to its high tolerance to 1,4-DAB.However,C.glutamicumlacks the native pathway for 1,4-DAB biosynthesis as well as catabolic pathway.By heterogeneous expression of ornithine decarboxylase fromE.coli,1,4-DAB was successfully detected in the engineeredC.glutamicumstrain.In combination with the deletion of L-arginine repressor ArgR and the L-ornithine transcarbamoylase ArgF,the 1,4-DAB titer reached 6 g·L-1with a yield of 0.12 g 1,4-DAB per g glucose [11].However,ArgF deletion requires the extra supplementation of L-arginine for stain growth,which increased the fermentation cost and simultaneously induced a strong feedback inhibition on the N-acetylglutamate kinase (ArgB).Thus,a plasmid-based system was developed to fine-tune ArgF expression,which improved the 1,4-DAB titer to 19 g·L-1with a yield of 0.16 g 1,4-DAB per g glucose,which is the highest 1,4-DAB titer reported so far using theC.glutamicumplatform [30,31].

Several engineering strategies have also been performed for further improving 1,4-DAB production.As one of the key elements,ODC was screened and rationally engineered.Seven ODCs originating from different organisms were comparably analyzed inC.glutamicum.As a result,it was found that the ODC fromEnterobacter cloacaedisplayed the highest activity for 1,4-DAB production [7].The catalytic efficiency of ODCs could also be improved by protein engineering.For example,ODC fromE.coliwas designed using a structure-based rational approach.Two residues,I163 and E165 were identified to be important for increasing substrate binding affinity.Through the introduction of two mutations (I163T/E165T),ODC activity was increased by 62.5-fold [12].

The identification of the potential targets responsible for improving 1,4-DAB titer is another alternative approach for developing efficient 1,4-DAB overproducers.Using a systematic gene deletion approach,thecg1722gene responsible for 1,4-DAB acetylation inC.glutamicumwas identified and designated assnaA.Deletion of genesnaAprevented the accumulation of byproduct Nacteylputrescine and resulted in a 41%increase in 1,4-DAB production [18].Transcriptome analysis revealed that increased expression in thecgmARoperon encoding a putative permease and a transcriptional TetR-family repressor responded to 1,4-DAB overproduction inC.glutamicum[18].Deletion of genecgmRincreased 1,4-DAB production by 19%,and the overexpression of genecgmAincreased 1,4-DAB production by 24% [18].In another study,the transcriptional profiling during the production of 1,4-DAB in an engineeredC.glutamicumstrain were also analyzed and some potential genetic targets were provided.Accordingly,overexpression of pyruvate carboxylase genepycor its mutantpyc458,and reduction of α-ketoglutarate decarboxylase (Kgd) activity significantly improved 1,4-DAB production[19].Furthermore,repressing ATP-consuming enzyme encoding genes (carB,xylB,accDA,purL,coaA,pknG,andpanC2) and NADPH-consuming enzyme encoding genes (dxr,aroE,andtrxB) to enhance ATP and NADPH supply was also confirmed as an efficient strategy to improve 1,4-DAB production [19].

Whole genome resequencing of an evolved 1,4-DAB producingC.glutamicumstrain indicated that single nucleotide polymorphisms existed inodhAgene [7].The gene expression in pentose phosphate and anaplerotic pathways,the glyoxylate cycle,and the L-ornithine biosynthesis pathway was upregulated,while the expression of genes involved in the aspartate family,aromatic,and branched chain amino acid and fatty acid biosynthetic pathways were downregulated in the evolvedC.glutamicumthrough a comparative proteomic analysis [7].Accordingly,the evolvedC.glutamicumwas further engineered by reducing OdhA expression through changingodhAnative start codon,and overexpressingcgmAorpyc458genes,and 1,4-DAB titer was improved to 12.4 g/L [7].In another study,a genome-scale stoichiometric model was built for a 1,4-DAB producingC.glutamicum.Through the flux balance analysis,several potential targets for improving1,4-DAB production were identified.Followed by the engineering of glycolysis,2-oxoglutarate dehydrogenase activity,proline biosynthesis,1,4-DAB N-acetylation and feedback control of L-arginine biosynthesis,1,4-DAB production was significantly enhanced[18].These studies provide insights into the further development of 1,4-DAB overproducers.

2.3.1,5-Diaminopentane

2.3.1.Whole-cell bioconversion

1,5-DAP is a C5 platform chemical that is biosynthesized by the decarboxylation of L-lysine.Nowadays,bio-based 1,5-DAP has been synthesizedviathe whole-cell bioconversion or the direct fermentation process.To obtain efficient whole-cell biocatalysts,the engineeredE.colithat overexpressed LDCs from different organisms includingE.coli,Hafnia alvei,Klebsiella oxytoca,andKlebsiella pneumoniawas developed as a workhorse for 1,5-DAP production(Table 1).For example,E.coli cadAgene was employed to be overexpressed inE.colito develop the whole-cell biocatalysts,and 142.8 g·L-1of 1,5-DAP was obtained from L-lysine with a molar yield of 80%[32].Use of a recombinantE.colistrain overexpressingE.coli ldcCgene achieved a 1,5-DAP titer of 110.16 g·L-1at a productivity of 11.42 g·(L-1·h-1) and a molar yield of 83.3% [8].Whole-cell biocatalysts ofE.coliXBHaLDC were prepared by expressing LDC fromH.alvei,and 136 g·L-1of 1,5-DAP could be produced from L-lysine with a molar yield of 97%[9].For whole cell biocatalysts,one of the most prominent bottlenecks is the limitation in mass transfer due to the catalysts’ cell membrane.LLysine uptake and 1,5-DAP excretion system have been well described inE.coli.They include thecadBgene encoding Llysine/1,5-DAP antiporter that is responsible for 1,5-DAP excretion in coordination with L-lysine uptake [33].To address the mass transfer problem during 1,5-DAP biosynthesis,CadB was overexpressed and optimized by fusion with the signal peptide of PelB in a recombinantE.colistrain expressing CadA.1,5-DAP production of 221 g·L-1was achieved from bioconversion of L-lysine at a productivity of 55.25 g·(L-1·h-1)and a molar yield of 92%,the highest 1,5-DAP titer reported so far [17].

Currently,biological production of 1,5-DAP based on the wholecell biotransformation process has been produced at the industrial scale by Cathay Industrial Biotech (Shanghai,China) and Ningxia EPPEN Biotech (Ningxia,China) [34].In addition,Ajinomoto(Tokyo,Japan) is working on the industrial production of biobased 1,5-DAP by the enzymatic decarboxylation of L-lysine.

2.3.2.1,5-DAP production via the fermentation strategy

Employing the whole-cell biocatalysts offers the advantage of high 1,5-DAP production.However,the use of L-lysine as the raw material increases the production cost compared to the cost of sugar.For the sustainable bioproduction of 1,5-DAP from renewable sugars,the development of 1,5-DAP fermentative overproducers is highly desirable.WithE.coliorC.glutamicumas the host,several metabolic engineering strategies for the efficient production of 1,5-DAP has been performed.

In wild-typeE.coli,1,5-DAP is not detectable [35].Qianet al.[36]first reported to engineerE.colifor overproducing 1,5-DAP in a glucose containing medium.In the engineeredE.coli,speE,speG,ygjG,andpuuAgenes involved in were deleted to block theendogenous 1,5-DAP degradation and utilization,andcadAanddapAgenes were overexpressed to enhance the flux into 1,5-DAP.The 1,5-DAP titer of 9.61 g·L-1was finally achieved by the engineeredE.coliat a productivity of 0.32 g·(L-1·h-1) using the fedbatch strategy[36].Based on this strain,the potential gene targets involved in improving 1,5-DAP production were screened based on a library of synthetic sRNAs.As a result,the repression of UDPNacetylmuramoyl-L-alanyl-D-glutamate-2,6-diaminopimelate ligase,encoded bymurEgene was identified to increase 1,5-DAP production by 55%.With a fed-batch cultivation strategy,12.6 g·L-1of 1,5-DAP was finally produced in the glucose medium [37].

Table 1 Summary of 1,5-DAP production performance by whole-cell bioconversion process

C.glutamicumis a promising host for the 1,5-DAP production due to its natural ability of high L-lysine production.LDCs fromE.coliencoded bycadAorldcCgenes have been employed for 1,5-DAP production inC.glutamicum.Mimitsuksaet al.[38]described that 2.6 g·L-11,5-DAP was successfully detected with a yield of 0.144 g per g glucose when thecadAgene was integrated into the genome ofC.glutamicum.This was the first report of 1,5-DAP fermentation by engineeredC.glutamicum.Thereafter,LdcC fromE.coliwas heterologously expressed inC.glutamicumfor the production of 1,5-DAP using a genome-based expression strategy under the control of strong constitutivetufpromoter.Moreover,the systems metabolic engineering ofC.glutamicumto improve 1,5-DAP production was also performed.Releasing the feedback inhibition of LysC and PycA by the expression of mutantslysC311andpycA458,improving the oxaloacetate supply by the overexpression ofpycAand deletion ofpck,enhancing the flux into 1,5-DAP by the overexpression oflysC,dapB,ddhandlysA,and attenuating flux into the competing threonine pathway by reducing homoserine dehydrogenase activity were accomplished.These events increased the 1,5-DAP titer produced by the final engineeredC.glutamicumto 30.6 g·L-1[39].Subsequently,the expression ofldcCwas optimized inC.glutamicumby regulating its strength with six different synthetic promoters.The highest production of 1,5-DAP was obtained whenldcCgene was expressed under the control of the PH30 promoter[40].In another study,ldcCgene under the optimal promoter PH30 was expressed in an expired industrial L-lysine-producingC.glutamicumby integration into thelysElocus of the chromosome,a gene that encodes the Llysine exporter.The final engineered strain achieved a 1,5-DAP titer of 103.78 g·L-1,which is the highest level reported to date[41].

Several other efforts were also performed for the further development of superior 1,5-DAP producer.For example,it was found that 20% of the 1,5-DAP undergoes acetylation reaction in the engineeredC.glutamicum.To identify the gene responsible for acetylation of 1,5-DAP inC.glutamicum,six candidates,which are annotated as proteins with acetyltransferase activity in the genome ofC.glutamicum,were targeted[42].An acetyltransferase encoded byNCgl1469was characterized with 1,5-DAP acetylation.When theNCgl1469gene was deleted in an engineeredC.glutamicumDAP-4,the accumulation of N-acetyldiaminopentane was avoided in the medium,and a 1.1-fold increase in the yield of 1,5-DAP was achieved[42].In addition,LDC activity inC.glutamicumwas suggested to be inhibitedin vivoby the end-product 1,5-DAP.With the genome-widetranscriptionalprofilingofa1,5-DAPoverproducing strain,a permease,encoded bycg2893,was identified to be responsible for 1,5-DAP secretion [43].Deletion ofcg2893could result in the 90% reduction of 1,5-DAP secretion.When thecg2893gene was overexpressed,the 1,5-DAP yield was increased by 20%,and the accumulation of byproduct N-acetyldiaminopentane was reduced by 75% [43].In another study,CadB fromE.coliwas co-expressed with LdcC fromH.alveiinC.glutamicumto improve 1,5-DAP secretion.As a result,1,5-DAP yield and extracellular 1,5-DAP were increased by 30% and 73%,accompanying with a 22% increase in 1,5-DAP secretion rate,respectively [44].

To decrease the production cost of 1,5-DAP,its microbial production from low cost substrates has been explored for the development of a sustainable process.For example,Buschkeet al.,explored the production of 1,5-DAP from lignocellulose-derived xylose.Through the heterologous expression of thexylAandxylBgenes fromE.coli,the 1,5-DAP-producingC.glutamicumwas also engineered for the use of xylose.The generatedC.glutamicumDAP-Xyl1 exhibited efficient production of 1,5-DAP from xylose and from mixtures of xylose and glucose.The 1,5-DAP production of the engineered strain in industrially relevant hemicellulose fractions was also tested based on a two-step process involving the enzymatic hydrolysis of hemicellulose and 1,5-DAP fermentation[45].However,the 1,5-DAP yield and productivity were significantly reduced using the pentose sugar.To address this problem,thein vivoandin silicometabolic flux analysis by13C was performed together with elementary modes to identify bottlenecks in the PPP and the TCA that negatively affected performance on xylose.In combination with the global transcriptomics analysis,thetktoperon,fructose bisphosphatase(encoded byfbp),isocitrate dehydrogenase (encoded byicd),L-lysine exporter(encoded bylysE)and N-acetyl diaminopentane(encoded byact)were targeted.All the model-predicted targets were then implemented into the genome of the basic producerC.glutamicumDAPXyl1,and yieldedC.glutamicumstrain DAP-Xyl1icdGTG Peftufbp PsodtktΔactΔlysE,which was designated C.glutamicumDAP-Xyl2.Cultivation of C.glutamicumDAP-Xyl2 on minimal xylose medium resulted in a 54%increase of the 1,5-DAP yield and a 100%increase in productivity.The engineered stain finally accumulated 103 g·L-1of 1,5-DAP from xylose with a yield of 32% via a fed-batch process [46],the highest titer obtained to date on xylose.In this work,the 1,5-DAP titer on xylose was almost the same as the highest level reported on glucose,and has opened future options towards biopolyamides from non-food raw materials.

Methanol,a one-carbon compound,has attracted increasing attentions to be used as an available substrate for large-scale bioproduction of fuels and chemicals,as it can be easily derived from natural gas[47,48].Methanol production is approximately 60 million metric tons annually[49].Both wild-typeE.coliandC.glutamicumlack the methanol assimilation pathways.Through employing the ribulose monophosphate (RuMP) pathway,C.glutamicumwas engineered to use methanol as an auxiliary carbon source by heterologous expression of MDH fromB.methanolicus,and HPS and PHI fromB.subtilis.A higher cell density of the engineeredC.glutamicumwas achieved when it was cultivated in the methanol containing medium[50].Subsequently,a 1,5-DAP producingC.glutamicumwas engineered for co-utilization of methanol.After assembly of the methanol assimilation pathway consisting of MDH,HPS,and PHI,and deletion of the genesaldandfadHresponsible for formaldehyde oxidation,13C-label from methanol was successfully traced to the secreted product 1,5-DAP [51].The example demonstrated the potentiality of bioconversion of methanol to diamine in synthetic methylotrophic strain.

For fermentation of biobased diamines,glucose as carbon resource was a common strategy for fermentation(Table 2).However,glucose made by food resource is not an ideal carbon source for production.Thus,non-food raw materials have been employed to production diamines (Table 3).The titer of diamines yet to be improved,though non-food raw materials have been a successful method.

2.4.Aliphatic diamines with longer carbon chains

Table 3 Summary of diamines production performance from non-food raw materials

The possibility that biotechnologically produced other diamines with longer carbon chains was also explored.1,6-diaminohexane,a six carbon diamine,is in high industrial demand due to its use as a monomer for the production of polyamide 6,6 and 6,10.Lauet al.[52]developed a seven-step process for the bioconversion of (S)-2-amino-6-oxopimelate into 1,6-diaminohexane.For the fermentative production of 1,6-diaminohexane,several non-natural metabolic pathways have been proposed.For example,Botes and Conradie demonstrated a biochemical pathway for producing 1,6-diaminohexane,which relies on CoA-dependent elongation enzymes or analogues enzymes associated with the carbon storage pathways from polyhydroxyalkanoate accumulating bacteria [53].

Long-chain diamines having more than six carbons can be used as monomers for polyamides with low moisture absorption and high mechanical resistance [54].With the whole cell biotransformation approach,Klatte and Wendisch designed a strain ofE.coliW3110/pTrc99A-ald-adh that could produce various non-natural diamines from corresponding alcohols by the heterologous expression of alanine dehydrogenase fromBacillus subtilis,alcohol dehydrogenase fromBacillus stearothermophilus,and ω-transaminase fromV.fluvialis.In the system,L-alanine and NH4Cl were also supplemented as amino group donor for amination and redox cofactor recycling.As a result,microbial production of 1,8-diaminoctane,1,10-diaminodecane,and 1,12-diaminododecane was realized with conversion yields of 87,100,and 60%,respectively [55].Similarly,Sunget al.developed a parallel anti-sense cascade reaction for the synthesis of α,ω-diamines from their corresponding α,ω-diols with an engineeredE.colistrain expressing a aldehyde reductase and a ω-transaminase as the whole-cell biocatalysts.Based on this system,1,8-diaminoctane,1,10-diaminodecane,and 1,12-diaminododecane were produced with conversion yields of 96,57,and 39%,respectively [56].Until now,metabolic pathway of long-chain diamines from renewable carbon sources has not been reported yet.In addition,the chemical-catalytic conversion of some biomass also could give the production of long-chain diamines.For example,1,10-decanediamine (1,10-DDA) could be chemically converted from sebacic acid derived from castor oils[57].

3.Aromatic Diamines

Aromatic diamines are also key building blocks in industry.With the fast development of bio-based aliphatic diamines,the synthesis of bio-based aromatic diamines from resourable biomasses has been performed in recent years.Lignin,and cashew nut shell are the main sources of renewable aromatic compounds.The synthesis of aromatic diamines based on these renewable biomasses are summarized here (Fig.2).

3.1.Aromatic diamines derived from lignin

Among them,lignin is the most abundant source of biorenewable aromatics and thus regarded as an ideal feedstock for producing bioaromatic chemicals.For example,with the lignin as the starting material,the commercial production of vanillin has been achieved[23,58].Starting from vanillin,three amine functionalization compunds,including 3-((2-aminoethyl)thio)propyl-4-(3-((2a minoethyl) thio) propoxy)-3-methoxybenzoate,and 2-((3-((4-(3-((2-aminoethyl)thio)propoxy)-3-methoxybenzyl)oxy)propyl)thio)e than-1-amine were succefully synthesized(Fig.2A and 2B)[22].In addition,Llevotet al.,[21]developed an efficient rounte to produce highly pure divanillin from vanillin through enzymatic catalysis.Based on the divanillin,two bio-based aromatic diamines of methylated divanillylamine (Fig.2C) and 3,4-dimethoxydianiline(Fig.2D) were successfully synthesized and characterized and tested as curing agents for the design of bio-based epoxy thermosets [59].

3.2.Aromatic diamines derived from cashew nut shell

Cashew nut shell liquid is a highly attractive renewable resource for synthesis of aromatic difunctional monomers due to its unique structural features,abundant availability and low cost[60,61].Starting from cashew nut shell liquid,cardanol could be generated through the distillation under reduced pressure,which takes advantage of the three reactive sites,namely,phenolic hydroxyl,aromatic ring and unsaturation(s) in the alkenyl side chain.As the certain outstanding properties of cardanol,it is considered as an desirable materials for synthesizing difunctional monomers [60,61].Numberous aromatic diamines based on cardanol have been synthesized and their utility for preparation of aromatic polyimides was demonstrated.For example,Jadhavet al.created an aromatic diamine with a long spacer by reacting cardanol monoaminated with 4,4′-dichlorodiphenyl sulfone [62](Fig.2E).Shingteet alsynthesized a partially bio-based aromatic diamine 1,1-bis(4-aminophenyl)-3-pentadecylcyclohexane starting from cardanol [63](Fig.2F).Sadavarteet al.first removed the phenol function of the saturated cardanol then performed the nitration and the reduction to obtain an aromatic diamine [64](Fig.2G).

3.3.Aromatic diamines derived from terpenoids

Terpenoids,produced from pine resin,are sustainable hydrocarbons that can potentially be used to synthesize aromatic compounds [65].In the presence of water,hydrogen cyanide,and sulfuric acid at low temperature,McKeeveret al.successfully sythesized menthane diamine(MNDA)[66](Fig.2H),a primary alicyclic diamine in which both amino groups are attached to tertiary carbon atoms.From terpenoid-derived p-cymene,a bisaniline 4,4′-methylenebis(5-isopropyl-2-methylaniline was obtained [67](Fig.2I).

4.Application of Bio-Based Diamines

Diamines have been widely used as the as the monomer for the synthesis of polyamide and polyurethane as shown in Fig.3.Among the above mentioned diamines,bio-based 1,4-DAB and 1,5-DAP revealed the most industrialization prospect.Their application in the synthesis of polyamide and polyurethane has attracted people’s increasing interest.

Fig.2.Structures of bio-based aromatic diamines.(A) 3-((2-aminoethyl)thio)propyl-4-(3-((2aminoethyl) thio) propoxy)-3-methoxybenzoate;(B) 2-((3-((4-(3-((2-aminoethyl)thio)propoxy)-3-methoxybenzyl)oxy)propyl)thio)ethan-1-amine;(C) methylated divanillylamine;(D) 3,4-dimethoxydianiline;(E) An aromatic diamine with a long spacer;(F) 1,1-bis(4-aminophenyl)-3-pentadecylcyclohexane;(G) 4,4’-((sulfonylbis(4,1-phenylene)bis(oxy))bis(2-pentadecylaniline) (H) menthane diamine;(I) 4,4’ -methylenebis(5-isopropyl-2-methylaniline).

Fig.3.Application of bio-based diamines in the synthesis of polyamides and polyurethanes.

Polyamides,also known as nylons,have a wide range of applications in automotive,electrical,and textile industries and also in the medical sector [1,68].The two best known petroleumbased polyamides,polyamide 6 (PA6) and polyamide 6.6 (PA 6.6),have been commercially available for decades,and shared an annual global market size of USD 25.66 billion in 2017 (https://www.grandviewresearch.com/industry-analysis/nylon-6–6-market).With the increasing concerns over sustainable polyamides within recent decades,bio-polyamides account for approximately 5% of the current biopolymer market.The development of bioproduction process for diamines would further promote the market of bio-polyamides.Bio-based 1,4-DAB could replace petroleum-based 1,4-DAB to synthesize PA4.6,PA4.10,and PA4T by polycondensation with adipic acid,sebacic acid,andp-phthalic acid respectively.The fully bio-based polyamide PA 4.10 has already commercially available trademarked as EcoPaxx (DSM,The Netherlands).

Based on the bio-based 1,5-DAP,bio-based polyamides such as PA5.2,PA 5.6,and PA 5.10 [9,41,69],have been produced through polymerization with appropriate bio-blocks such as succinate,glutaric acid [70],adipic acid [71],and sebacic acid [72].Comparison of the material properties with the commercial polymers including Ultramid B27 (PA6) and Ultramid A27 (PA6.6) revealed that 1,5-DAP-derived polyamides exhibit excellent tensile strength,high melting points,and resistance to organic solvents.Thus,they could replace PA 6.6 or PA6 in many applications[9,41,69].For example,compared to PA6 and PA6.6,PA 5.10 possesses lower water absorption and density,higher degradation temperature and glass transition temperature,and superior mechanical properties.The lower density makes PA 5.10 particularly suitable to be used in energyfriendly transportation.The higher degradation temperature of the bio-based PA 5.10 indicated it can be used as a heat resistant material suitable for some harsh thermal environments.The biobased PA5.6 presents a good balance between chemical resistance,wear and abrasion resistance,mechanical,and thermal properties,and serves as a competitive novel fiber for textile material[73,74].The higher water absorption PA5.6 makes it particularly attractive for some applications such as fibers,that can provide more comfort in wear ability.The lower glass transition temperature compared to conventional PA6.6 makes PA5.6 good temperature resistance[75].The synthesis of other novel bio-based polyamindes,such as PA5.2 [76]or PA5.20 [77]was also tested.PA5.2 was synthesized from dibutyl oxalate and 1,5-DAP.Compared with commercially available polyamide,PA52 has a high melting temperature,low water absorption,good mechanical properties and excellent crystallization characteristics,which made it well suited for the production of high-performance parts in the automobile and electronics industries.Overall,the high-performance PA5.X has great potential to compete with and replace fossil-fuel-based polyamides (e.g.,PA6 and PA6.6) in the near future.The generation of these new polyamines would address a more enormous market of polyamides.

Polyurethanes are among the most important and versatile polymers and are widely applied in coatings,adhesives,medicinal products,foams,paints,ink binders,and biomaterials [78–81].In addition to polyamines,diamines are also important materials for the synthesis of polyurethanes through the intermediate diisocyanates.With the bio-based 1,5-DAP,the production of 1,5-pentamethylene diisocyanate (PDI) has been tested through the phosgenation reaction[82].Corresponding hydrophilized counterparts of PDI,such as the waterborne coatings (Desmodur?eco N 7300,Covestro AG) and waterborne polyurethane (WPU) dispersions has been successfully synthesized[83].The test of properties indicated the performance of PDI in terms of surface dry time,flexibility,impact resistance,pencil hardness and diesel resistance are comparable with HDI.More importantly,as the new type of highgrade polyurethane monomer material,the PDI-derived coatings exhibit higher drying speed than the HDI-derived coatings,more suitable applied in the furniture and machinery industry.Overall,bio-based PDI is an ideal alternative for HDI from fossil fuel.

5.Conclusions and Future Perspective

In this review,the production of bio-based diamines including 1,3-diaminopropane,putrescine,cadaverine,1,6-diaminohexane,1,8-diaminooctane,1,10-diaminodecane,1,12-diaminododecane and several aromatic diamines are summarized.Many challenges remain to be overcome to achieve the the industrialization of bio-based diamines.First,the efficiency of producing microorganisms should be further improved.During the fermentation,the accumulation of diamines in the fermentation medium was toxic to the cell growth and limited the final product yield.However,few studies have adressed the inhibition mechanism of diamines.Further studies on the damage mechanism of diamines are urgently desired for the development of robust diamine producers.Second,understanding of the regulation networks is needed to redesign the regulatory circuits or to regulate gene targets to improve diamine production.Third,the enzyme activity involved in the synthesis of diamines should be further improved.In addition,the synthetic route for several aliphatic and aromatic diamines should be further improved.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by the National Key Research and Development Program of China (Grant No.2018YFA0901500),National Nature Science Foundation of China (Grant No.21606127,Grant No.21706126),and Jiangsu synergetic innovation center for advanced bio-manufacture (Grant No.XTB1802,Grant No.XTE1844).