Production of (R)-3-Quinuclidinol by E. coli Biocatalysts Possessing NADH-Dependent 3-Quinuclidinone Reductase (QNR or bacC) from Microbacterium luteolum and Leifsonia Alcohol Dehydrogenase (LSADH)

Isotani, Kentaro; Kurokawa, Junji

doi:10.3390/ijms131013542

Cited by 18 publications

(4 citation statements)

References 24 publications

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“…While impressive, these procedures usually suffer from some disadvantages including the high cost of chiral metal catalysts, subsequent removal of trace metals, the oftentimes lengthy process for screening and synthesis ligand, and the unsatisfactory ≤50% yield for enzymatic resolution. To establish a renewable alternative to these chemical processes, biocatalytic routes to ( R )-3-quinuclidinol using wild-type , or engineered microorganisms − have been described. But most of them proceed at low product titer, even only 2 g/L, and needed a prolonged conversion time.…”

Section: Introductionmentioning

confidence: 99%

A Tailor-Made Self-Sufficient Whole-Cell Biocatalyst Enables Scalable Enantioselective Synthesis of (R)-3-Quinuclidinol in a High Space-Time Yield

Chen

Xie

Zhou

et al. 2019

Org. Process Res. Dev.

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A self-sufficient two-in-one whole-cell biocatalyst combining ketoreductase and cofactor regenerating enzyme activities has been developed and successfully utilized to synthesize (R)-3-quinuclidinol with an increase in the reaction rate of 3-fold over the native enzymes at low biocatalysts loading (∼1.65%), excellent enantioselectivity, impressive substrate concentration of 486 g L −1 , and high space-time yield of (R)-3-quinuclidinol up to 1505.5 g L −1 d −1 , which was the highest ever reported. These results demonstrated that the newly developed self-sufficient biocatalyst could be useful for synthetic and industrial application in synthesis of (R)-3-quinuclidinol, essential for the production of solifenacin, revatropate, and aclidinium, with better clinical outcome than those currently available.

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Section: Introductionmentioning

confidence: 99%

A Tailor-Made Self-Sufficient Whole-Cell Biocatalyst Enables Scalable Enantioselective Synthesis of (R)-3-Quinuclidinol in a High Space-Time Yield

Chen

Xie

Zhou

et al. 2019

Org. Process Res. Dev.

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“…菌株 Microbacterium luteolum JCM 9174 [214] , 需要乙醇脱氢酶和 NADH 降解酶的协同作用. 图式 4 3-quinuclidinone 的生物转化途径 [214] Scheme 4 Possible pathway conversion of 3-quinuclidinone [214] Ikunaga 等 [215] [216] 总共有 16 个目, 43 个科 [217]…”

Section: 海洋中其它来源的稀有放线菌unclassified

New Natural Products of Rare Actinomycetes from 2006 to 2018

Zhang¹,

Yang²,

Zhou³

et al. 2019

Chin. J. Org. Chem.

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The microbe is an important source of lead compound. It plays an important role in drug development. Many new active compounds were found from actinomycetes, and the number of new compounds from rare actinomycetes showed an upward trend. This paper introduces the new active compounds including 515 new natural products found in rare actinomycetes, from plants, soil, marine sediment, marine animals and so on. The structure type included macrolides, polyketides, anthraquinones, bipyridines, polyene, etc. The biotransformation of natural products by rare actinomycetes was reported from January 2006 to June 2018.

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“…Bacterial ADHs are most often produced in Escherichia coli (Isotani et al 2012;Zhou et al 2013;Li et al 2012) due to its capability to produce proteins in high concentrations, in a short time and at low cost. In addition, endogenous ADHs have low activities so that modified E. coli can be easily used as whole-cell catalysts with high yields and ee without the problem of by-products (Hildebrandt et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Coexpression of Lactobacillus brevis ADH with GDH or G6PDH in Arxula adeninivorans for the synthesis of 1-(R)-phenylethanol

Rauter¹,

Prokoph

Kasprzak

et al. 2014

Appl Microbiol Biotechnol

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The yeast Arxula adeninivorans was used for the overexpression of an ADH gene of Lactobacillus brevis coding for (R)-specific alcohol dehydrogenase (LbADH) to synthesise enantiomerically pure 1-(R)-phenylethanol. Glucose dehydrogenase gene from Bacillus megaterium (BmGDH) or glucose 6-phosphate dehydrogenase of Bacillus pumilus (BpG6PDH) were coexpressed in Arxula to regenerate the cofactor NADPH by oxidising glucose or glucose 6-phosphate. The yeast strain expressing LbADH and BpG6PDH produced 5200 U l(-1) ADH and 370 U l(-1) G6PDH activity, whereas the strain expressing LbADH and BmGDH produced 2700 U l(-1) ADH and 170 U l(-1) GDH activity. However, the crude extract of both strains reduced 40 mM acetophenone to pure 1-(R)-phenylethanol with an enantiomeric excess (ee) of >99 % in 60 min without detectable by-products. An increase in yield was achieved using immobilised crude extracts (IEs), Triton X-100 permeabilised cells (PCs) and permeabilised immobilised cells (PICs) with PICs being most stable with GDH regeneration over 52 cycles. Even though the activity and synthesis rate of 1-(R)-phenylethanol with the BpG6PDH and LbADH coexpressing strain was higher, the BmGDH-LbADH strain was more stable over successive reaction cycles. This, combined with its higher total turnover number (TTN) of 391 mol product per mole NADP(+), makes it the preferred strain for continuous reaction systems. The initial non-optimised semi-continuous reaction produced 9.74 g l(-1) day(-1) or 406 g kg(-1) dry cell weight (dcw) day(-1) isolated 1-(R)-phenylethanol with an ee of 100 % and a TTN of 206 mol product per mole NADP(+). In conclusion, A. adeninivorans is a promising host for LbADH and BpG6PDH or BmGDH production and offers a simple method for the production of enantiomerically pure alcohols.

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Production of (R)-3-Quinuclidinol by E. coli Biocatalysts Possessing NADH-Dependent 3-Quinuclidinone Reductase (QNR or bacC) from Microbacterium luteolum and Leifsonia Alcohol Dehydrogenase (LSADH)

Cited by 18 publications

References 24 publications

A Tailor-Made Self-Sufficient Whole-Cell Biocatalyst Enables Scalable Enantioselective Synthesis of (R)-3-Quinuclidinol in a High Space-Time Yield

A Tailor-Made Self-Sufficient Whole-Cell Biocatalyst Enables Scalable Enantioselective Synthesis of (R)-3-Quinuclidinol in a High Space-Time Yield

New Natural Products of Rare Actinomycetes from 2006 to 2018

Coexpression of Lactobacillus brevis ADH with GDH or G6PDH in Arxula adeninivorans for the synthesis of 1-(R)-phenylethanol

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