Bioproduction of Enantiopure (R)‐ and (S)‐2‐Phenylglycinols from Styrenes and Renewable Feedstocks. Issue 7 (21st December 2020)

• Record Type: Journal Article
• Authors: Sekar, Balaji Sundara; Mao, Jiwei; Lukito, Benedict Ryan; Wang, Zilong; Li, Zhi
• Is Part Of: Advanced synthesis & catalysis. Volume 363:Issue 7(2021)
• Page Start: 1892
• Page End: 1903
• Publication Date: 2020-12-21
• Subjects: Amino alcohols -- Biocatalysis -- Enantioselectivity -- Enzyme catalysis -- One-pot reaction -- Renewable resources; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.202001322
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: Enantiopure ( R )‐ and ( S )‐2‐phenylglycinols are important chiral building blocks for pharmaceutical manufacturing. Several chemical and enzymatic methods for their synthesis were reported, either involving multi‐step synthesis or starting from a relatively complex chemical. Here, we developed one‐pot simple syntheses of enantiopure ( R )‐ and ( S )‐2‐phenylglycinols from cheap starting materials and renewable feedstocks. Enzyme cascades consisting of epoxidation‐hydrolysis‐oxidation‐transamination were developed to convert styrene 2 a to ( R )‐ and ( S )‐2‐phenylglycinol 1 a, with butanediol dehydrogenase for alcohol oxidation as well as BmTA and NfTA for ( R )‐ and ( S )‐enantioselective transamination, respectively. The engineered E. coli strains expressing the cascades produced 1015 mg/L ( R )‐1 a in >99% ee and 315 mg/L ( S )‐1 a in 91% ee, respectively, from styrene 2 a . The same cascade also converted substituted styrenes 2 b –k and indene 2 l into substituted ( R )‐phenylglycinols 1 b –k and (1 R, 2 R )‐1‐amino‐2‐indanol 1 l in 95–>99% ee . To transform bio‐based L ‐phenylalanine 6 to ( R )‐1 a and ( S )‐1 a, ( R )‐ and ( S )‐enantioselective enzyme cascades for deamination‐decarboxylation‐epoxidation‐hydrolysis‐oxidation‐transamination were developed. The engineered E. coli strains produced ( R )‐1 a and ( S )‐1 a in high ee at 576 mg/L and 356 mg/L, respectively, from L ‐phenylalanine 6, as the first synthesis of these compounds from a bio‐based chemical. Finally, L ‐phenylalanine biosynthesis pathway was combined with ( R )‐ or ( S )‐enantioselective cascade in one strain or coupled strains, to achieve the first synthesis of ( R )‐1 a and ( S )‐1 a from a renewable feedstock. The coupled strain approach enhanced the production, affording 274 and 384 mg/L ( R )‐1 a and 274 and 301 mg/L ( S )‐1 a, from glucose and glycerol, respectively. The developed methods could be potentially useful to produce these high‐value chemicals from cheap starting materials and renewable feedstocks in a green and sustainable manner. Abstract :