Department of Biotechnology, Central University of Haryana, Haryana, 123031, Mahendergarh, India.
Biomanufacturing and Process Development Laboratory, School of Biotechnology, Jawaharlal Nehru University, 110067, New Delhi, India.
Appl Biochem Biotechnol. 2023 Nov;195(11):6881-6892. doi: 10.1007/s12010-023-04442-9. Epub 2023 Mar 23.
Lipstatin, natural inhibitor of pancreatic lipase produced by Streptomyces toxytricini and used as an anti-obesity drug. Chemical mutagenesis was performed with different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (NTG) for strain improvement to obtain high yield of lipstatin. It was observed that the potential of the wild type strain to produce lipstatin (1.09 g/L) was very low. Selected mutants produced lipstatin in the range of 1.20-2.23 g/L at the flask level where maximum amount of lipstatin was produced by M5 mutant. For comparative study, both the parent and M5 mutant strain of S. toxytricini were grown at the lab scale bioreactor with suitable sources of carbon and nitrogen. Significant increase in the production of lipstatin was observed at the bioreactor level where the wild type strain produced 2.4 g/L of lipstatin, while through the NTG mutation, the production of lipstatin was 5.35 g/L. However, Dry Cell Weight (DCW) of the mutant strain was less in comparison with wild type strain and significant morphological differences were observed. Nearly 5 times increase in the production of lipstatin was achieved through NTG mutation and bioreactor-controlled conditions. It was determined that the NTG treatment might be beneficial for strain improvement to get a better candidate for lipstatin production on commercial scale.
利普司他汀，一种天然的胰腺脂肪酶抑制剂，由绛红色链霉菌（Streptomyces toxytricini）产生，被用作减肥药。为了提高利普司他汀的产量，采用不同浓度的 N-甲基-N'-硝基-N-亚硝基胍（NTG）对菌株进行化学诱变。结果表明，野生型菌株产生利普司他汀的潜力非常低（1.09 g/L）。筛选出的突变株在摇瓶水平上产生的利普司他汀在 1.20-2.23 g/L 范围内，其中 M5 突变株产生的利普司他汀最多。为了进行比较研究，将绛红色链霉菌的亲本和 M5 突变株分别在实验室规模的生物反应器中，使用合适的碳源和氮源进行培养。在生物反应器水平上观察到利普司他汀的产量显著增加，野生型菌株产生 2.4 g/L 的利普司他汀，而通过 NTG 突变，利普司他汀的产量达到 5.35 g/L。然而，与野生型菌株相比，突变株的干细胞重量（DCW）较少，并且观察到明显的形态差异。通过 NTG 突变和生物反应器控制条件，利普司他汀的产量增加了近 5 倍。结果表明，NTG 处理可能有利于菌株改良，从而在商业规模上获得更好的利普司他汀生产候选菌株。
