Ye Ruifang, Wang Qian, Zhou Xiaofang
Department of Bioengineering, East China University of Science and Technology, Shanghai, China.
Bioprocess Biosyst Eng. 2009 Jun;32(4):521-9. doi: 10.1007/s00449-008-0272-y. Epub 2008 Oct 31.
Based on the report that the introduction of the biosynthetic precursor of lincomycin, propylproline, could increase the production of lincomycin (Bruce et al. in US Patent 3,753,859, 1973), a mutant strain pro10-20, with resistance of feedback suppression of proline (an analog of propylproline) was thus selected and lincomycin production increased by 10%. The addition of three amino acids (L-proline, L-tyrosine, L-alanine) which are the precursors of propylproline to the fermentation medium was found to enhance the accumulation of L-dopa through different pathways and was favorable to lincomycin biosynthesis. The production of lincomycin was increased by 23, 10, 13%, respectively, with the addition of 0.05 g L(-1) L-proline at 60 h, 0.005 g L(-1) L-tyrosine and 0.1 g L(-1) L-alanine directly in the medium.
基于林可霉素生物合成前体丙基脯氨酸的引入可提高林可霉素产量的报道（Bruce等人，美国专利3,753,859，1973年），因此筛选出了对脯氨酸（丙基脯氨酸的类似物）反馈抑制具有抗性的突变菌株pro10-20，林可霉素产量提高了10%。研究发现，向发酵培养基中添加作为丙基脯氨酸前体的三种氨基酸（L-脯氨酸、L-酪氨酸、L-丙氨酸），可通过不同途径增强L-多巴的积累，有利于林可霉素的生物合成。在培养基中分别直接添加0.05 g L(-1) L-脯氨酸（在60小时时添加）、0.005 g L(-1) L-酪氨酸和0.1 g L(-1) L-丙氨酸后，林可霉素的产量分别提高了23%、10%、13%。
