Abstract
BackgroundAs well known, both natural and synthetic steroidal compounds are powerful endocrine disrupting compounds (EDCs) which can cause reproductive toxicity and affect cellular development in mammals and thus are generally regarded as serious contributors to water pollution. Streptomyces virginiae IBL14 is an effective degradative strain for many steroidal compounds and can also catalyze the C25 hydroxylation of diosgenin, the first-ever biotransformation found on the F-ring of diosgenin.ResultsTo completely elucidate the hydroxylation function of cytochrome P450 genes (CYPs) found during biotransformation of steroids by S. virginiae IBL14, the whole genome sequencing of this strain was carried out via 454 Sequencing Systems. The analytical results of BLASTP showed that the strain IBL14 contains 33 CYPs, 7 ferredoxins and 3 ferredoxin reductases in its 8.0 Mb linear chromosome. CYPs from S. virginiae IBL14 are phylogenetically closed to those of Streptomyces sp. Mg1 and Streptomyces sp. C. One new subfamily was found as per the fact that the CYP Svu001 in S. virginiae IBL14 shares 66% identity only to that (ZP_05001937, protein identifer) from Streptomyces sp. Mg1. Further analysis showed that among all of the 33 CYPs in S. virginiae IBL14, three CYPs are clustered with ferredoxins, one with ferredoxin and ferredoxin reductase and three CYPs with ATP/GTP binding proteins, four CYPs arranged with transcriptional regulatory genes and one CYP located on the upstream of an ATP-binding protein and transcriptional regulators as well as four CYPs associated with other functional genes involved in secondary metabolism and degradation.ConclusionsThese characteristics found in CYPs from S. virginiae IBL14 show that the EXXR motif in the K-helix is not absolutely conserved in CYP157 family and I-helix not absolutely essential for the CYP structure, too. Experimental results showed that both CYP Svh01 and CYP Svu022 are two hydroxylases, capable of bioconverting diosgenone into isonuatigenone and β-estradiol into estriol, respectively.
Highlights
As well known, both natural and synthetic steroidal compounds are powerful endocrine disrupting compounds (EDCs) which can cause reproductive toxicity and affect cellular development in mammals and are generally regarded as serious contributors to water pollution
The number of cytochrome P450 genes (CYPs) is identical to that in S. avermitili and almost two times as that in S. coelicolor A3(2) and S. peucetius ATCC27952 (18 and 19 CYPs, respectively). Such high level of CYP diversity suggests the high diversity of the secondary metabolism pathways in S. virginiae IBL14
It’s worth noting that the Svu001 presumably belongs to a new CYP family since no close homologue is found in Genbank except that in Streptomyces sp
Summary
Both natural and synthetic steroidal compounds are powerful endocrine disrupting compounds (EDCs) which can cause reproductive toxicity and affect cellular development in mammals and are generally regarded as serious contributors to water pollution. Most of the ORFs of CYP have three distinct characteristics used often for their identification and CYPs have been confirmed existing in all eukaryotic (human, animals, plants, fungi, etc.) and prokaryotic organisms (bacteria, archaea, and even in viruse) [5,6,7,8]. They often are monooxygenases involved in oxidation of a range of endogenous compounds, such as cholesterol, lipids and steroidal hormones, as well as xenobiotics such as drugs and toxic chemicals in environment [9,10,11]. CYP genes responsible for secondary metabolism are often laid in antibiotic biosynthetic gene clusters to catalyze stereo- and region- specific reaction of substrates to related derivatives
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