Pig­ments that can do more

The elu­cid­a­tion of the struc­ture and ori­gin of the so-called ​“Yel­low Affin­ity Sub­stance” (YAS) provides new insights into cel­lu­lose degrad­a­tion by the bac­teri­um Clostridi­um ther­mo­cel­lum (new name: Acet­ivi­brio ther­mo­cel­lus). It is assumed that the yel­low pig­ment plays a decis­ive role in the con­ver­sion of plant bio­mass into usable sug­ar, which opens up new per­spect­ives for bio­fuel pro­duc­tion. The study also opens up new approaches in anti­bi­ot­ics research.

Anaer­obic bac­teria were among the first life forms on earth and exis­ted at a time when there was no oxy­gen in the atmo­sphere. While many organ­isms depend on an oxy­gen-rich envir­on­ment to sur­vive, anaer­obes thrive in places where oth­ers can­not – in com­pletely oxy­gen-free hab­it­ats such as the human gut or the ocean floor. The enzymes of these bac­teria are even sens­it­ive to oxy­gen. Their remark­able adapt­ab­il­ity is increas­ingly attract­ing the atten­tion of researchers.

Anaer­obic bac­teria often pro­duce unusu­al sub­stances. This makes them par­tic­u­larly inter­est­ing for research and bio­tech­no­logy, for example for the pro­duc­tion of anti­bi­ot­ics or bio­fuels. They are also indis­pens­able play­ers in the nat­ur­al nutri­ent cycle by break­ing down organ­ic mater­i­al such as cel­lu­lose and releas­ing nutri­ents back into the ecosystem.

A sig­nal sub­stance with a key role

Clostridi­um ther­mo­cel­lum is one of the best-known anaer­obic microbes when it comes to the degrad­a­tion of cel­lu­lose – the main com­pon­ent of plant cell walls. It con­verts cel­lu­lose into sug­ar, which can then be used to pro­duce bio­fuels such as eth­an­ol. A con­spicu­ous yel­low pig­ment pro­duced by the bac­teri­um (YAS – Yel­low Affin­ity Sub­stance) plays a key role in this pro­cess. YAS pref­er­en­tially attaches itself to cel­lu­lose fibers. It is assumed that YAS helps to dir­ect the degrad­ing enzymes pre­cisely to where cel­lu­lose is present.

Struc­tur­al ana­lys­is of bac­teri­al pigments

Research­ers at the Leib­n­iz Insti­tute for Nat­ur­al Product Research and Infec­tion Bio­logy – Hans Knöll Insti­tute (Leib­n­iz-HKI) and the Max Planck Insti­tute for Chem­ic­al Eco­logy in Jena have now suc­ceeded for the first time in elu­cid­at­ing the molecu­lar com­pos­i­tion of YAS. The sci­ent­ists dis­covered that YAS con­sists of sev­er­al com­pon­ents, so-called cel­lux­an­thenes, and determ­ined their molecu­lar struc­tures using spec­tro­scop­ic ana­lyses (NMR, MS) and iso­tope labeling exper­i­ments. In addi­tion, they iden­ti­fied the bio­syn­thet­ic gene cluster respons­ible through tar­geted genet­ic manipulation.

A pig­ment with med­ic­al potential?

Sur­pris­ingly, the pig­ments show an effect against cer­tain microor­gan­isms. The cel­lux­an­thenes have mild anti­bi­ot­ic activ­ity against Gram-pos­it­ive bac­teria – includ­ing clin­ic­ally rel­ev­ant, res­ist­ant patho­gens. Under­stand­ing the genet­ic basis of bio­syn­thes­is also opens up the pos­sib­il­ity of pro­du­cing or modi­fy­ing cel­lux­an­thenes in the future. First authors Keishi Ishida and Jana Krabbe see prom­ising res­ults: ​“Although the yel­low pig­ments have been known for almost a cen­tury, their struc­ture has remained a mys­tery until now. We can now begin to invest­ig­ate pos­sible eco­lo­gic­al func­tions, includ­ing anti­bac­teri­al activ­ity to defend the food source (cel­lu­lose) against competitors.”

A step towards a sus­tain­able future

The dis­cov­ery and char­ac­ter­iz­a­tion of cel­lux­an­thenes bridges the gap between our under­stand­ing of micro­bi­al meta­bol­ism and prac­tic­al applic­a­tions in the energy sec­tor – and per­haps in future med­ic­al research. The find­ings could also help to optim­ize the use of plant biomass.

The research is part of the ​“Anoxy­Gen” pro­ject, for which Chris­ti­an Her­tweck was awar­ded one of the pres­ti­gi­ous ERC Advanced Grants from the European Research Coun­cil. Her­tweck is head of depart­ment at the Leib­n­iz-HKI and pro­fess­or at the Friedrich Schiller Uni­ver­sity Jena. ​“Anoxy­Gen aims to unlock the hid­den poten­tial of anaer­obic bac­teria to pro­duce new bio­act­ive nat­ur­al products,” explains Her­tweck. ​“Many of these microor­gan­isms carry genes in their gen­ome for the pro­duc­tion of valu­able com­pounds, but these usu­ally remain inact­ive under stand­ard labor­at­ory con­di­tions.” The team is devel­op­ing new molecu­lar bio­lo­gic­al meth­ods to activ­ate these hid­den bio­syn­thet­ic path­ways – meth­ods that pre­vi­ously exis­ted mainly for aer­obic (oxy­gen-depend­ent) microbes. The aim is to dis­cov­er and har­ness pre­vi­ously unknown nat­ur­al sub­stances with med­ic­al or bio­tech­no­lo­gic­al value. Anoxy­Gen com­bines mod­ern syn­thet­ic bio­logy with the dis­cov­ery of act­ive sub­stances and could open up new pos­sib­il­it­ies for phar­ma­ceut­ic­al development.

The Anoxy­Gen pro­ject also con­trib­utes to the Cluster of Excel­lence ​“Bal­ance of the Micro­ver­se”, which invest­ig­ates the com­plex sig­nal­ing and com­mu­nic­a­tion mech­an­isms with­in micro­bi­al com­munit­ies that gov­ern life on Earth.