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作 者:Xuemei Li Rui Zhang Jianjiong Li Jinhui Feng Qiaqing Wu Dunming Zhu Yanhe Ma
出 处:《Systems Microbiology and Biomanufacturing》2023年第4期585-592,共8页系统微生物学与生物制造(英文)
基 金:supported by the National Key R and D Program of China(NO.2019YFA0905300);National Natural Science Foundation of China(No.32171477);Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-001 and TSBICIP-PTJJ-007).
摘 要:Cholesterol and phytosterols can be served as the substrates for Actinobacteria to produce the precursors used in the synthesis of steroidal medicines.Cytochrome P450s from CYP125 and CYP142 families initiates the metabolism of cholesterol and/or phytosterols.In this study,we demonstrate the functional redundancy and substrate preference of five cytochrome CYP125s and CYP142s by the unmarked cyp genes deletion strains of Mycobacterium neoaurum NRRL B-3805.CYP125-3 was found to be responsible for the catalytic hydroxylation of both cholesterol and the C24-branched side-chains of phytosterols,while CYP142-2 can only oxidize cholesterol and/or cholest-4-en-3-one.The strain harboring the CYP125-3 produced 6.47 g l^(-1)and 5.13 g l^(-1)of 4-androstene-3,17-dione(AD)when 15 g l^(-1)cholesterol or 17.5 g l^(-1)phytosterols used,respectively.While,the strain harboring the CYP142-2 produced 7.10 g l^(-1)AD when 15 g l^(-1)cholesterol used.The other three cytochrome P450s have a smaller contribution for the degradation of cholesterol and phytosterols.CYP125-3 has the hydroxylation activity on more substrates than that of CYP142-2.This study provided possible guidance to improve the efficiency of AD and other metabolites production from different kinds of sterols by the genetic manipulation.
关 键 词:Sterol degradation Mycobacterium neoaurum Steroid C26/C27 monooxygenase Cytochrome CYP125s and CYP142s
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