PMID: 9647795Jul 2, 1998Paper

Structure-activity study of the lantibiotic mutacin II from Streptococcus mutans T8 by a gene replacement strategy

Applied and Environmental Microbiology
P ChenP W Caufield

Abstract

Mutacin II, elaborated by group II Streptococcus mutans, is a ribosomally synthesized and posttranslationally modified polypeptide antibiotic containing unusual thioether and didehydro amino acids. To ascertain the role of specific amino acid residues in mutacin II antimicrobial activity, we developed a streptococcal expression system that facilitates the replacement of the mutA gene with a single copy of a mutated variant gene. As a result, variants of mutacin II can be designed and expressed. The system was tested by constructing the following mutant peptides: delta N1, V7A, P9A, T10A, T10S, C15A, C26A, and C27A. All of these mutacin II variants except delta N1 and T10A, which were not secreted, were isolated, and their identities were verified by mass spectrometry. Variants P9A, C15A, C26A, and C27A failed to exert antimicrobial activity. Because the P9A and T10A variants comprise the "hinge" region of mutacin II, these observations suggest that in addition to the thioether and didehydro amino acids, the hinge region is essential for biological activity and biosynthesis or export of the peptide. Tandem mass spectrometry of the N-terminal part of the wild-type molecule and its C15A variant confirmed that the threonine at posi...Continue Reading

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Citations

Jul 4, 2003·Applied and Environmental Microbiology·Christiane SzekatGabriele Bierbaum
Jan 2, 2004·Microbiology·Haijie XiaoLiandong Huan
Sep 11, 2007·Journal of Molecular Microbiology and Biotechnology·Jun-ichi NagaoKenji Sonomoto
Aug 1, 2009·Natural Product Reports·John A McIntoshEric W Schmidt
Jun 1, 2011·Probiotics and Antimicrobial Proteins·Adam Pepperney, Michael L Chikindas
May 24, 2000·The Journal of Biological Chemistry·R E KrullP W Caufield
Aug 10, 2000·Biopolymers·A GuderH G Sahl
May 13, 2009·Molecular Microbiology·Mohammad R IslamK Sonomoto
Aug 28, 2012·Bioengineered·Paul D Cotter
Jun 13, 2020·Microbiology Resource Announcements·Indranil Biswas
Sep 11, 2007·Journal of Molecular Microbiology and Biotechnology·Fang ChengPer E J Saris
Nov 14, 2006·FEMS Microbiology Reviews·Alain DufourJean-Paul Le Pennec
May 18, 2007·Annual Review of Microbiology·Joanne M Willey, Wilfred A van der Donk
Nov 26, 2010·Molecular Microbiology·Des FieldR Paul Ross
Nov 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Amanda L McClerrenWilfred A van der Donk
May 22, 2007·The Journal of Biological Chemistry·Bo Li, Wilfred A van der Donk
Aug 8, 2018·FEMS Microbiology Reviews·Jeella Z AcedoMarco J van Belkum
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Aug 15, 2009·ACS Chemical Biology·Trent J Oman, Wilfred A van der Donk
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Oct 21, 2006·Chemistry & Biology·Champak ChatterjeeWilfred A van der Donk
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Apr 28, 2009·Journal of Bioscience and Bioengineering·Sikder M Asaduzzaman, Kenji Sonomoto
Jan 31, 2004·Science·Lili XieWilfred A van der Donk

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