From natural products discovery to commercialization: a success story

From natural products discovery to commercialization: a success story
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DOI:
10.1007/s10295-005-0076-x
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发表时间:
2006-07-01
影响因子:
3.4
通讯作者:
Dernain, Arnold L.
Dernain, Arnold L.
中科院分区:
工程技术3区
文献类型:
--
作者:
Dernain, Arnold L.

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为了使天然产品成为商业现实,必须对其生产过程进行实验室改进,因为野生菌株产生的效价永远无法与合成化学的力量相竞争。通过诱变进行菌株改良已取得重大成功。它主要是通过“蛮力”筛选或选择进行的,但近年来现代基因技术已经进入现场。对于每一个基因开发的新菌株,都有进一步的机会通过培养基修饰来提高滴度。主要关注的是通过诱导进行营养控制,以及通过碳源、氮源、磷酸盐源和终产物进行抑制和阻遏。菌株改良和营养改良都有助于新工艺的发展,然后由生化工程师将其扩大到中试规模,然后进入工厂规模的发酵罐。
In order for a natural product to become a commercial reality, laboratory improvement of its production process is a necessity since titers produced by wild strains could never compete with the power of synthetic chemistry. Strain improvement by mutagenesis has been a major success. It has mainly been carried out by "brute force" screening or selection, but modern genetic technologies have entered the scene in recent years. For every new strain developed genetically, there is further opportunity to raise titers by medium modifications. Of major interest has been the nutritional control by induction, as well as inhibition and repression by sources of carbon, nitrogen, phosphate and end products. Both strain improvement and nutritional modification contribute to the new process, which is then scaled up by biochemical engineers into pilot scale and later into factory size fermentors.