Enhanced production of ansamitocin P-3 by addition of isobutanol in fermentation of Actinosynnema pretiosum.
Supply of isobutanol to enhance the production of anti-tumor agent ansamitocin P-3 (AP-3) in medium containing agro-industrial residues was investigated with analysis of gene transcription, enzyme activity, and intermediate accumulation. Under the optimal addition of isobutanol, about 4-fold improvement of AP-3 production was obtained, and the consumption of isobutanol and accumulation of isobutyrate, malonyl-CoA, and acetyl-CoA were observed. Compared to the control without isobutanol addition, activities of both isobutanol dehydrogenase and valine dehydrogenase were enhanced in isobutanol supplemented culture. Transcription level of genes in AP-3 biosynthetic and isobutyryl-CoA catabolic pathways responded to isobutanol addition in a similar way as AP-3 biosynthesis. It is concluded that isobutanol addition was an effective strategy for increasing AP-3 production via regulation of gene transcription and pools of precursors, and the information obtained might be helpful to the fermentation productivity improvement on large scale.
Lin
Jinxia
J
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Bai
Linquan
L
Deng
Zixin
Z
Zhong
Jian-Jiang
JJ
D000192:Actinomycetales / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D000440:Butanols / Q000494:pharmacology*; D005285:Fermentation / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000235:genetics; D008453:Maytansine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D010088:Oxidoreductases / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000214:Acyl Coenzyme A; D000440:Butanols; D008453:Maytansine; C050106:isobutyryl-coenzyme A; C040507:isobutyl alcohol; C015682:ansamitocins; D010088:Oxidoreductases