Improvement of industry-applied rifamycin B-producing strain, Amycolatopsis mediterranei, by rational screening.

Jin, Zhi Hua; Lin, Jiusheng; Xu, Zhinan; Cen, Pei Lin

doi:10.2323/jgam.48.329

Cited by 24 publications

(16 citation statements)

References 12 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the biosynthesis of microbial secondary metabolites, inhibition by high concentrations of the precursors or products is usually the main limitation [30][31][32]. In this work, the mutation conferring higher tolerance for raw epothilone products or the precursor mixture were produced and selected for.…”

Section: Mutants With Resistance To Epothilone and Its Precursorsmentioning

confidence: 99%

Mutation and a high-throughput screening method for improving the production of Epothilones of Sorangium

Gong¹,

Sun²,

Liu³

et al. 2007

J Ind Microbiol Biotechnol

View full text Add to dashboard Cite

The epothilones are highly promising prospective anticancer agents that are produced by the myxobacterium Sorangium cellulosum. We mutated the epothilone producing S. cellulosum strain So0157-2 to improve the production of epothilones. For evaluation in high-throughput of a large number of mutants, we developed a simple microtiter method for primary screening. Using the classical UV-mutation method plus selection pressures, the production capacity was increased about 0.5 approximately 2.5 times the starting strain. The mutants with higher production and different phenotypes were further subjected to recursive protoplast fusions and the fusants products were screened under multi-selection pressure. Furthermore, the production was greatly increased by the genome shuffling. For epothilone B, the production of one fusant was increased about 130 times compared to the starting strain, increasing from 0.8 mg l(-1) to 104 mg l(-1).

show abstract

Section: Mutants With Resistance To Epothilone and Its Precursorsmentioning

confidence: 99%

Mutation and a high-throughput screening method for improving the production of Epothilones of Sorangium

Gong¹,

Sun²,

Liu³

et al. 2007

J Ind Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…[59] Rifamycin Bi so btained on an industrial scale by fermentation from Amycolatopsis mediterranei with ay ield of up to 19 gL À1 . [60] It is then used for preparation of the semisynthetic antibacterials 32-34 ( Figure 5). Similar to the erythronolides,the chirallycomplex macrocyclic scaffold of rifamycin B (31)w as retained and synthetic chemistry focussed on selective manipulationofo ne of the side chains.…”

Section: Rifamycinsmentioning

confidence: 99%

“…Building block B2 (compound 67)w as prepared from piperidine 59 which was alkylated with p-chloronitrobenzene (60) and reduced by catalytic hydrogenation to provide aniline 62. Reactiono f62 with phenyl chloroformate gave carbamate 63, Scheme8.Synthesis of everolimus (46)f rom sirolimus (45).…”

Section: Itraconazolementioning

confidence: 99%

Drug Syntheses Beyond the Rule of 5

Tyagi

Begnini

Poongavanam

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

Drugs in the chemical space beyond the rule of 5 (bRo5) can modulate targets with difficult binding sites while retaining cell permeability and oral absorption. Reviewing the syntheses of bRo5 drugs approved since 1990 highlights synthetic chemistry's contribution to drug discovery in this space. Initially, bRo5 drugs were mainly natural products and semi‐synthetic derivatives. Later, peptidomimetics and de novo designed compounds, that include up to seven chiral centres and macrocyclic rings became dominant. These drugs are prepared by total synthesis, sometimes by routes of more than 25 steps with stereocentres originating from the chiral pool, or being installed by chiral induction or enzymatic resolution. Interestingly, ring‐closing metathesis proved to be the method of choice for macrocyclisation in hepatitis C virus protease inhibitors. We conclude that structural simplification, planning of synthetic routes regarding incorporation of stereocentres and macrocyclisation, as well as incorporation of structural knowledge and consideration of chameleonic properties in design, should facilitate drug discovery in bRo5 space.

show abstract

“…Rational screening allows for a significant improvement in the efficiency of the selection process. Thus, precursorresistant mutants and precursor analog-resistant mutants are widely used for screening high producing strain (Jin et al 2002a(Jin et al , b, 2006Parekh et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Improvement of milbemycin-producing Streptomyces bingchenggensis by rational screening of ultraviolet- and chemically induced mutants

Wang

Xiang

2009

World J Microbiol Biotechnol

View full text Add to dashboard Cite

Milbemycin antibiotics are produced by Streptomyces hygroscopicus subsp. aureolacrimosus and a newly isolated Streptomyces bingchenggensis, respectively. According to the biosynthetic pathway of milbemycins generated by S. hygroscopicus subsp. aureolacrimosus, a rational screening procedure with UV irradiation and N-methyl-N 0 -nitroso-N-nitrosoguanidine (NTG) mutation was performed to obtain high milbemycin-producing S. bingchenggensis. Aminoacetic acid (Glycine)-resistant mutants (AA r ), propionate-resistant mutants (PRP r ), streptomycin-resistant mutants (STR r ) and 2-deoxy-D-glucoseresistant mutants (DOG r ) were selected successively. A strain S. bingchenggensis BC-109-6 with AA r , PRPr, STR r and DOG r was obtained and its production of milbemycin A3 and A4 reached 1,450 lg/ml, which was 80% higher than that of the ancestral strain S. bingchenggensis BC-101-4. The subculture experiments indicated that the hereditary characteristic of high productivity of S. bingchenggensis BC-109-6 was stable. The production of milbemycin A3 and A4 by S. bingchenggensis BC-109-6 in a 50-l fermentor could reach 1,380 lg/ml after 360 h batch fermentation.

show abstract

Improvement of industry-applied rifamycin B-producing strain, Amycolatopsis mediterranei, by rational screening.

Cited by 24 publications

References 12 publications

Mutation and a high-throughput screening method for improving the production of Epothilones of Sorangium

Mutation and a high-throughput screening method for improving the production of Epothilones of Sorangium

Drug Syntheses Beyond the Rule of 5

Improvement of milbemycin-producing Streptomyces bingchenggensis by rational screening of ultraviolet- and chemically induced mutants

Contact Info

Product

Resources

About