Zwittermicin A is an antibiotic that has been identified from the bacterium
Bacillus cereus UW85.
[Haiyin, He (April, 1994) "Zwittermicin A, an Antifungal and Plant Protection Agent from Bacillus cereus", Tetrahedron Letters 35 (16) 2499-2502 doi=10.1016/S0040-4039(00)77154-1] It is a molecule of interest to agricultural industry because it has the potential to suppress plant disease due to its broad spectrum activity against certain gram positive and gram negative
prokaryotic micro-organisms. The molecule is also of interest from a metabolic perspective because it represents a new structural class of antibiotic and suggests a crossover between
polyketide and non-ribosomal peptide biosynthetic pathways. Zwittermicin A is linear aminopolyol.
Biosynthesis
Zwittermycin A
biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
is a hybrid of polyketide and non-ribosomal peptide synthetic pathways. Most likely, all of the synthases are located on one megasynthase much like a type I fatty acid synthase. Based on mutant studies, the biosynthetic cluster involved in zwittermicin production has been identified and the pathway has been proposed. The
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s responsible for the production of zwittermicin A are located on a 16 kb cluster containing nine orfs and a self resistant gene zmaR, a
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
that encodes an
acylation enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that deactivate zwittermicin A.
The hybrid
synthase In biochemistry, a synthase is an enzyme that catalyses a synthesis process.
Note that, originally, biochemical nomenclature distinguished synthetases and synthases. Under the original definition, synthases do not use energy from nucleoside tripho ...
used in zwittermicin A production utilizes modified extender units such as hydroxymalonyl-ACP, aminomalonyl-ACP and
2,3-diaminopropionate. Therefore, many of the genes in the biosynthetic cluster encode for
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s responsible for the synthesis of these extender units used in the hybrid synthase. For example, orf5 encodes ZWA5A, an enzyme that is responsible for the PLP mediated amination that converts L-serine to 2,3-diaminopropionate. It has also been shown that orf5, orf7, orf4 and orf6 participate in the biosynthesis of aminomalonyl-ACP and orf3, orf2 and orf1 synthesize hydroxymalonyl-ACP.
Gene organization of the Zwittermicin A biosynthetic cluster.
Genes encoding for the seven component hybrid synthase responsible for the assembly of the backbone is likely located on the largest gene, orf8. Assembly begins by the activation of a serine residue. This is done by tethering the amino acid to a peptidal carrier protein via a non-ribosomal peptide synthetase. Subsequently elongation of an activated malonyl unit covalently attached to an acyl carrier protein by a ketosynthase occurs giving the five carbon unit. The next two elongation steps proceed in a similar manner using aminomalonyl and hydroxymalonyl units from a second and third ketosynthase. Finally, condensation of 2,3-diaminopropionate with the carried molecule by a second nonribosomalpeptide synthase produces the zwittermicin A backbone. Attack of ammonia via an amidotransferase enzyme releases the carrier protein. The last step involves a carbomyltransferase enzyme that carbamolates the released molecule giving the final product.
[{{cite journal , vauthors=Emmert EA, Klimowicz AK, Thomas MG, Handelsman J , title=Genetics of zwittermicin a production by Bacillus cereus , journal=Appl. Environ. Microbiol. , volume=70 , issue=1 , pages=104–13 , date=January 2004 , pmid=14711631 , pmc=321298 , doi= 10.1128/AEM.70.1.104-113.2004]
Footnotes
Antibiotics