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29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955

Paper ID Volume ID Publish Year Pages File Format Full-Text
20047 43155 2015 6 PDF Available
Title
29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955
Abstract

Maklamicin is a spirotetronate-class antibiotic produced by Micromonospora sp. NBRC 110955, and a polyketide assembly line and a glycerate utilization system are involved in its biosynthesis. One tailoring step in the biosynthesis is predicted to be post-polyketide synthase (PKS) modification, which seems to be catalysed by putative cytochrome P450 monooxygenases, MakC2 and/or MakC3. In this study, we characterized makC2 and makC3 in the biosynthesis of maklamicin and identified a new maklamicin analogue from a makC2 disruptant. Gene deletion of makC2 resulted in the complete loss of maklamicin production with concomitant accumulation of a new compound (29-deoxymaklamicin), while gene deletion of makC3 did not affect the maklamicin production, indicating that 29-deoxymaklamicin is an intermediate in the biosynthetic pathway of maklamicin and should serve as the substrate of MakC2. 29-Deoxymaklamicin showed strong-to-modest anti-microbial activity against gram-positive bacteria. The fact that Streptomyces avermitilis heterologously expressing makC2 successfully converted 29-deoxymaklamicin into maklamicin confirmed that MakC2 is the final-step hydroxylase in the formation of mature maklamicin.

Keywords
Micromonospora; Spirotetronate-class antibiotics; Maklamicin; Cytochrome P450; Hydroxylation
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29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically engineered strain of Micromonospora sp. NBRC 110955
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 120, Issue 6, December 2015, Pages 608–613
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us